A

PROJECT REPORT
ON
“Overview of the Diagnosis, Treatment and Medicines in Prostate Cancer”
Submitted To:
Mahamuda Fatema
(Lecturer)
Department of Pharmacy
Northern university Bangladesh
Submitted By:
Abdur Rahman Sopan Mohamad Palash Ahmed
ID: 05200101724 ID: 05200101677
Abrar Zaber Tasin Noray Afzal Nahid
ID: 05200101696 ID: 05200101724
Atia Anam Simi
ID: 05200101745

Department of Pharmacy
Northern University Bangladesh
 DECLARATION
This is to clarify that the BPH work entitled “Overview of the Diagnosis, Treatment and
Medicines in Prostate Cancer”
has been carried out by MD. Abdur Rahman (Sopan),
Abrar Zaber Tasin, Atia Anam Simi, Noray Afzal Nahid, Mohamad Palash Ahmed
in the Department of Pharmacy, Northern University Bangladesh.
The above work or any part of this work has not been submitted anywhere for the
reward of any degree or diploma.

Signature of Candidates Signature of Supervisor

…………………………. …………………………..
MD. Abdur Rahman (Sopan) Mahamuda Fatema
ID: (Lecturer)
Dept. of Pharmacy Department of Pharmacy
Northern University Bangladesh Northern University Bangladesh

……………………..
Abrar Zaber Tasin
ID: 05200101696
Dept. of Pharmacy
Northern University Bangladesh

……………………………..
Atia Anam Simi
ID: 05200101745
Dept. of Pharmacy
Northern University Bangladesh

……………………………
Noray Afzal Nahid
ID: 05200101724
Dept. of Pharmacy
Northern University Bangladesh

……………………………
Mohamad Palash Ahmed
ID: 05200101677
Dept. of Pharmacy
Northern University Bangladesh
 ACKNOWLEDGEMENT

Glory be to the Supreme, the Creator and Learn of the universe who's generosity sustains us
and lets us to pursue and finish our study in the pharmacy department “

We feel a profound sense of gratitude to our reverend supervisor Mahamuda Fatema,

Lecturer, Department of Pharmacy, Northern University Bangladesh for the day to day
supervision, constructive suggestion, valuable criticism and keen interest to carry out this project
work. His scientific integrity and dedication have been inspiring us through our graduate study
and his patience and continuous encouragement helped our scientific approaches during these
years.
It gives us immense pleasure to express appreciation and gratitude to Professor Dr. Md. Harun
Ar Rashid, Head of the Department of Pharmacy and Northern University Bangladesh for
their invaluable assistance and motivation.
We also extend our sincere gratitude to our parents, family, and well-wishers for their
unwavering inspiration over the project's duration.

May Allah reward each and every one of them.

 ABSTRACT
Prostate Cancer is the leading cause of cancer deaths in men around the world. With an
anticipated 1,414,000 new cases and 375,304 deaths from prostate cancer in 2020, it is the
second most prevalent cancer diagnosed and the fifth leading cause of cancer death among men
globally.
Over the past 20 years, there has also been an increase in prostate cancer cases in Bangladesh. In
Bangladesh, 773 persons lost their lives to prostate cancer in 2018, marking a 1.5% rise in the
number of deaths from the disease.
Prostate cancer claimed 1,664 lives in Bangladesh in 2020, accounting for 0.23% of total
fatalities.
Bangladesh was rated 173rd in the world with an age-adjusted prostate cancer death rate of 3.07
per 100,000 persons.
The objective of the project is to give a thorough review of the various prostate cancer
treatments, including diagnostic, treatment options, and medications.
Information regarding diagnosis, treatment, and medications is gathered from many websites and
publications.
After examining the data gathered from these sources, we have narrowed down our selection of
medications to those with fewer adverse effects and a positive outlook for the future.
 Table of Content

SL. NO. Topics Name Page No.

1.1 Introduction
1.1 INTRODUCTION
Prostate Cancer
What is prostate cancer?
Prostate cancer develops when abnormal cells in the prostate gland grow in an uncontrolled way,
forming a malignant tumour (ref: Cancer Council). The global burden of prostate cancer is
substantial, ranking among the top five cancers for both incidence and mortality (Ferlay et al.
2015). Prostate cancer is a major cause of disease and mortality among men, and each year 1.6
million men are diagnosed with and 366,000 men die of prostate cancer. There is a 40-fold
difference in age-adjusted incidence rates between men with the highest (African-American men
in the United States) and lowest (Asian men living in their native countries) incidence (Ferlay et
al. 2013; Howlader et al. 2016). Prostate cancer incidence and mortality rates increase among
men who migrate from low-risk (e.g., Asia) to high-risk (e.g., United States) countries compared
with those in their native countries, although rates remain below the host countries’ rates
(Shimizu et al. 1991; Yu et al. 1991). Prostate cancer is the fifth most common cause of cancer
death globally, accounting for an estimated 366,000 deaths and 6.3 million disability-adjusted
life years in 2015 (Global Burden of Disease Cancer Collaboration 2016). It is the second most
common cause of cancer death among men in the United States (Howlader et al. 2016).
Prostate cancer has the highest 5-year prevalence of any cancer type, accounting for 25% of all
prevalent cancers (Ferlay et al. 2013).

Understanding the prostate

The prostate is a sex gland in men. It's about the size of a walnut, but it can grow larger as men
age. It sits below the bladder and in front of the rectum. It surrounds the upper part of the urethra.
This is the tube that carries urine and semen out of the body. The prostate is part muscle and part
gland. It has ducts that open into the urethra.
The prostate gland’s main purpose is to secrete a fluid that makes up most of semen (the fluid
that carries sperm). Prostate fluid is made in the gland cells of the prostate. During a man’s
orgasm, the muscle parts of the prostate help to send the prostate fluid into the urethra. There, it’s
mixed with other fluids and sperm that were made in the testicles to form semen. The semen then
leaves the body through the penis during ejaculation (Ref: University of Rochester Medical
Center Rochester, NY)

1.2 Major causes of prostate cancer

Some factors that can increase your risk of prostate cancer include:
• age, increasing rapidly after 50 years of age
• family history of prostate, breast or ovarian cancer, especially BRCA1 and BRCA2 gene
mutations
• a father or brother diagnosed with prostate cancer before the age of 60.
There is an association with high testosterone levels. (Ref: Cancer council)

Symptoms of prostate cancer

• frequent urination
• pain while urinating
• blood in the urine or semen
• a weak stream
• pain in the back or pelvis
• weak legs or feet
More widespread disease often spreads to the bones and causes pain or unexplained weight loss
and fatigue.
(Ref: Cancer council)

1.3 Diagnosis and Treatment

The following tests must be done to make sure the presence of prostate cancer in a patient;
PSA blood test
A prostate specific antigen (PSA) blood test measures the PSA levels, the proteins made by both
normal and cancerous prostate cells. Because PSA levels can be variable, it is common for your
doctor to use results from more than one blood test, over time, to help determine your risk of
prostate cancer.

Some men with prostate cancer have normal PSA levels, and only one in three men with an
elevated PSA level has cancer. As it is not a definitive test, a PSA test is normally used with other
tests to diagnose prostate cancer. (Ref: Cancer council)
Digital rectal examination
Digital Rectal Examination (DRE) is no longer recommended as a routine test for men who do
not have symptoms of prostate cancer. As not all prostate cancers produce high levels of PSA, it
may still be used to check the prostate before doing a biopsy.
Biopsy
A biopsy is the main tool for diagnosing prostate cancer. A biopsy removes small pieces of tissue
from different parts of the prostate with the aid of a rectal ultrasound, for examination under
microscope. It is used to detect the disease and determine its aggressiveness (the Gleason score
of 1-5 is added from two samples to form a score out of 10; low scores of 6 or less, indicate slow
growing disease). (Ref : Cancer Council)
Transrectal magnetic resonance imaging (MRI)
A procedure that uses a strong magnet, radio waves, and a computer to make a series of detailed
pictures of areas inside the body. A probe that gives off radio waves is inserted into the rectum
near the prostate. This helps the MRI machine make clearer pictures of the prostate and nearby
tissue. A transrectal MRI is done to find out if the cancer has spread outside the prostate into
nearby tissues. This procedure is also called nuclear magnetic resonance imaging (NMRI).
Transrectal MRI may be used during a biopsy procedure. This is called transrectal MRI guided
biopsy. (Ref: [Link])
PSMA PET scan
An imaging procedure that is used to help find prostate cancer cells that have spread outside of
the prostate, into bone, lymph nodes, or other organs. For this procedure, a cell-targeting
molecule linked to a radioactive substance is injected into the body and travels through the
blood. It attaches to a protein called prostate-specific membrane antigen (PSMA) that is found on
the surface of prostate cancer cells. A PET scanner detects high concentrations of the radioactive
molecule and shows where the prostate cancer cells are in the body. A PSMA PET scan may be
used to help diagnose prostate cancer that may have come back or spread to other parts of the
body. It may also be used to help plan treatment. (Ref: [Link])
Transrectal ultrasound
A procedure in which a probe that is about the size of a finger is inserted into the rectum to
check the prostate. The probe is used to bounce high-energy sound waves (ultrasound) off
internal tissues or organs and make echoes. The echoes form a picture of body tissues called a
sonogram. Transrectal ultrasound may be used during a biopsy procedure. This is called
transrectal ultrasound guided biopsy. (Ref: [Link])
1.3 TREATMENT
There are different types of treatment for patients with prostate cancer.
Eight types of standard treatment;
• Watchful waiting or active surveillance
• Surgery
• Radiation therapy and radiopharmaceutical therapy
• Hormone therapy
• Chemotherapy
• Targeted therapy
• Immunotherapy
• Bisphosphonate therapy

New types of treatment are being tested in clinical trials.

• Cryosurgery
• High-intensity–focused ultrasound therapy
• Proton beam radiation therapy
• Photodynamic therapy
(Ref: National Cancer Institute)

2.0 Drugs Approved for prostate cancer:

❖ Abiraterone Acetate(Gen name)(Ref: National Cancer Institute)

Brand names:

Abiret (Drug International ltd) 250mg tablet

Abiron (Ziska Pharmaceuticals Ltd) Tablet 250 mg
Zytix (Beacon Pharmaceuticals PLC) Tablet 250 mg
Zytiga (UniMed UniHealth Pharmaceuticals Ltd) Tablet 250 mg
(ref: [Link])

❖ (Niraparib Tosylate Monohydrate) (Gen Name) (Ref: National Cancer Institute)

Brand Name:

Niranib Capsule 100 mg Everest Pharmaceuticals Ltd.

Nirova Capsule 100 mg Beacon Pharmaceuticals PLC
Ovaxa Capsule 100 mg Jenphar Bangladesh Ltd.
Paribac Capsule 100 mg Ziska Pharmaceuticals Ltd. (Ref: [Link])

❖ Apalutamide (gen name)(Ref: National Cancer institute)

Brand Name:
Apaluda Tablet 60 mg Beacon Pharmaceuticals PLC
Prostaxen Tablet 60 mg Everest Pharmaceuticals Ltd. (ref: [Link])
 ❖ Bicalutamide (gen name) (Ref: National Cancer institute)
Brand Name:

Bical Tablet 50 mg Beacon Pharmaceuticals PLC

Bicalon Tablet 50 mg Drug International Ltd.
Calumide Tablet 50 mg Healthcare Pharmaceuticals Ltd.
Casodex Tablet 50 mg AstraZeneca (ref: [Link])

❖ Cabazitaxel (Gen Name) (Ref: National Cancer institute)

Brand Name:

Jevtana IV Infusion 60 mg/1.5 ml Synovia Pharma PLC. (Mfg. by: Genzyme

Corporation) (ref: [Link])
 ❖ Camcevi (Leuprolide Mesylate) (Gen name) (Ref: National Cancer institute)
Brand Name:

Imanix Tablet 100 mg (Beacon Pharmaceuticals PLC)

Peflox Tablet 400 mg (Drug International Ltd.)

❖ Bicalutamide (GEN NAME)

Brand Name:
Bical Tablet 50 mg Beacon Pharmaceuticals PLC
Bicalon Tablet 50 mg Drug International Ltd
Calumide Tablet 50 mg Healthcare Pharmaceuticals Ltd.
 Casodex Tablet 50 mg AstraZeneca

❖ Darolutamide (Gen Name)

Brand Name:
Damid Tablet 300 mg Eskayef Pharmaceuticals Ltd.

❖ Degarelix (Gen Name)

Brand Name :
Firmagon SC Injection 80 mg vial

❖ Docetaxel (Gen Name)

Brand name:
Daxotel IV Infusion 20 mg vial (Drug International Ltd)

Docefrez IV Infusion 80 mg/vial Healthcare Pharmaceuticals Ltd.

 Docetor IV Infusion 20 mg/vial Eskayef Pharmaceuticals Ltd.

Taxedol IV Infusion 20 mg/vial Beximco Pharmaceuticals Ltd.

IV Infusion 80 mg/vial Renata Limited

❖ Eligard (Leuprolide Acetate) (Gen Name)

Brand Name:
Apit 40 mg (Drug International Ltd) megestrol Acetate

❖ Enzalutamide(Gen Name)

Brand Name:
Zaluta 40 mg Beacon Pharmaceuticals PLC

❖ Erleada (Apalutamide) (Gen Name) (ref: National Cancer institute)

Brand Name:
Prostaxen 60 mg (Everest Pharmaceuticals Ltd.)

Apaluda Tablet 60 mg Beacon Pharmaceuticals PLC

❖ Firmagon (Degarelix) (ref: National Cancer institute)

Brand Name:
Firmagon SC Injection SC Injection 80 mg/vial Radiant Pharmaceuticals Ltd.

(Mfg. by: Ferring Pharmaceuticals Ltd.) ref: medex

14. Flutamide (Gen Name)(ref: National Cancer institute)
Brand Name:
Proscan Tablet Tablet 250 mg Renata Limited
 ❖ Goserelin Acetate (Gen Name)(ref: National Cancer institute)

Brand Name: ref: medex

Golexin SC Injection (Goserelin 10.8 mg)

(Mfg. by: AMW GmbH)

❖ Leuprolide Acetate(ref: National Cancer institute)
Brand Name :
Lucrin Depot Injection (Leuprolide acetate 3.75mg)

☞ Unimed & Unihealth Manufacturers Ltd (Abbott Pharma Product)

Lucrin Depot Injection (Leuprolide acetate 11.25mg)

Unimed & Unihealth Manufacturers Ltd (Abbott Pharma Product)

❖ Leuprolide Mesylate(ref: National Cancer institute)

Brand Name:
CAMCEVI® ((leuprolide) 42 mg injection emulsion)

☞ U.S. specialty division of Intas Pharmaceuticals, Ltd

 ❖ Lynparza (Olaparib) (ref: National Cancer institute)
Brand Name: ref: medex
Inpoza Tablet 150 mg Genvio Pharma Ltd.

Tablet 150 mg Jenphar Bangladesh Ltd.

Olacent Tablet 100 mg Incepta Pharmaceuticals Ltd.

Olacent Tablet 150 mg Incepta Pharmaceuticals Ltd.
Olakin Tablet 150 mg Ziska Pharmaceuticals Ltd.

Olanib Tablet 150 mg Everest Pharmaceuticals Ltd.

Olanib Capsule 50 mg Everest Pharmaceuticals Ltd.
Olapar Tablet 100 mg Beacon Pharmaceuticals PLC

Tablet 150 mg Beacon Pharmaceuticals PLC

Olarigen Tablet 150 mg General Pharmaceuticals Ltd.

Olarigen Capsule 50 mg General Pharmaceuticals Ltd.

Olatab Tablet 100 mg Eskayef Pharmaceuticals Ltd.

Parib Capsule 50 mg Drug International Ltd.

 Parib Tablet 150 mg Drug International Ltd

❖ Mitoxantrone Hydrochloride(ref: National Cancer institute)

Brand Name:

Zocare Ophthalmic Solution (Antazoline + Tetryzoline

0.05%+0.04%) Healthcare Pharmaceuticals Ltd.
Doxorubicin Hydrochloride Liposome 20 mg/10 ml (ZAS Corporation) (Mfg. by: Dr.
Reddy's Laboratories Ltd, India)

23. Nilandron (Nilutamide) (ref: National Cancer institute)

Brand Name:
 Nigella Sativa [Black Seed Oil] 500 mg (Square Pharmaceuticals PLC.)

❖ Nubeqa (Darolutamide) (ref: National Cancer institute)

Brand Name:

Damid Tablet Darolutamide 300 mg (Eskayef Pharmaceuticals Ltd.)

❖ Olaparib(ref: National Cancer institute)

Brand Name:

Juparib Tablet 150 mg (Jenphar Bangladesh Ltd.)

Olapar Tablet 100 mg (Beacon Pharmaceuticals PLC)
26. Orgovyx (Relugolix) (ref: National Cancer institute)
Brand Name:
Religox Tablet 120 mg ACI Limited
Tablet 120 mg Square Pharmaceuticals PLC

Relugoli Tablet 120 mg Beacon Pharmaceuticals PLC

Relupros Tablet Tablet 120 mg Renata Limited

Rexilo Tablet 120 mg Incepta Pharmaceuticals Ltd.

❖ Pluvicto (Lutetium Lu 177 Vipivotide Tetraxetan) (ref: National Cancer institute)

☞ Brand Name: PLUVICTO®

☞ Manufacturer: Novartis

28. Provenge (Sipuleucel-T) (ref: National Cancer institute)

☞ Brand Name: PROVENGE®

☞ Manufacturer: Biomedicine
 ❖ Radium 223 Dichloride(ref: National Cancer institute)

☞ Brand Name: Xofigo

☞ Manufacturer: Bayer Healthcare

 ❖ Relugolix(ref: National Cancer institute)

☞ Brand Name: Religox Tablet (Relugolix 120 mg)

☞ Manufacturer: ACI Limited

☞ Brand name: Reluciba Tablet (Relugolix 120 mg)

☞ Manufacturer: Square Pharmaceuticals PLC

☞ Brand name: Relugoli Tablet (Relugolix 120 mg)

☞ Manufacturer: Beacon Pharmaceuticals PLC

☞ Brand Name: Relupros Tablet (Relugolix 120 mg)

☞ Manufacturer: Renata Limited

☞ Brand Name: Rexilo Tablet (Relugolix 120 mg)

☞ Manufacturer: Incepta Pharmaceuticals Ltd.

❖ Rubraca (Rucaparib Camsylate) (ref: National Cancer institute)

☞ Brand Name: Rubraca

☞ Manufacturer: pharmaand GmbH

❖ Taxotere (Docetaxel) (ref: National Cancer institute)

☞ Brand Name: Taxotere IV Infusion (Docetaxel Trihydrate 80 mg/vial)

☞ Manufacturer: Synovia Pharma PLC.

 ❖ Talazoparib Tosylate(ref: National Cancer institute)

☞ Brand Name: Talzenna

☞ Manufacturer: Pfizer Oncology Together™

Pfizer Oncology Together

❖ Talzenna (Talazoparib Tosylate) (ref: National Cancer institute)

Brand Name: TALZENNA®

☞ Manufacturer: Pfizer Oncology Together™

❖ Xofigo (Radium 223 Dichloride) (ref: National Cancer institute)

Brand Name:
Xofigo® Bayer HealthCare Pharmaceuticals Inc
 ❖ Xtandi (Enzalutamide) (ref: National Cancer institute)

Brand Name:
Enzalunix Tablet 40 mg Beacon Pharmaceuticals PLC

XTANDI
Astellas Pharma Ltd.

❖ Yonsa (Abiraterone Acetate) (ref: National Cancer institute)

Brand Name: YONSA Sun Pharmaceutical Industries, Inc.
 ❖ Zoladex (Goserelin Acetate) (ref: National Cancer institute)

Brand Name:
ZOLADEX® (Goserelin 10.8 mg)
MGH Healthcare Limited (Mfg. by: AstraZeneca)

❖ Zytiga (Abiraterone Acetate) (ref: National Cancer institute)

Brand Name:
ZYTIGA UniMed UniHealth Pharmaceuticals Ltd. (Mfg. by: Janssen-Cilag S.P.A. Italy)

3.0 Side Affects, Contraindications and Future perspective

Hormone Therapy in prostate cancer

Androgens (male sex hormones) are a class of hormones that control the development and
maintenance of male characteristics. The most abundant androgens in men are testosterone and
dihydrotestosterone (DHT).
Androgens are required for normal growth and function of the prostate.
Androgens promote the growth of both normal and cancerous prostate cells by binding to and
activating the androgen receptor, a protein that is expressed in prostate cells.
Ref:(National Cancer Institute)
Exact moment for using hormone therapy in prostate cancer:
• Along with radiation therapy as the first treatment for cancer that’s still in or around the
prostate, if the cancer is at higher risk for coming back after treatment
• Before radiation, to try to shrink the cancer to make treatment more effective
• If the cancer remains or comes back after treatment with surgery or radiation therapy
(especially if the cancer has spread, or if it’s not exactly clear where it is in the body)
• If the cancer has spread too far to be cured by surgery or radiation, or if you can’t have
these treatments for some other reason.
Side Effects of Hormone therapy of prostate cancer;
loss of interest in sex (lowered libido)
erectile dysfunction
hot flashes
loss of bone density
bone fractures
loss of muscle mass and physical strength
changes in blood lipids
insulin resistance
weight gain
mood swings
fatigue
growth of breast tissue (gynecomastia)
Ref: National Cancer Institute
Drugs used in Hormone therapy of prostate cancer:
• LHRH Antagonist:
• Leuprolide
Mild side effects: tiredness, hot flashes (a sudden wave of mild or intense body heat), sweating,
or clamminess, breast tenderness, pain, or change in breast size in both men and women, vaginal
discharge, dryness, or itching in women, spotting (light vaginal bleeding) or menstruation
(periods), decrease in size of testicles, decrease in sexual ability or desire, swelling of the hands,
feet, ankles, or lower legs, pain, burning, or tingling in the hands or feet, bruising, redness, or
hardening at place where injection was given, change in weight, muscle or joint pain, runny
nose, cough, sore throat, or flu-like symptoms, fever, stomach pain, constipation, headache, acne,
weakness, dizziness, nausea, increase in frequency of urination or having to urinate at night,
night sweats, hair loss.

Serious side effects: difficulty breathing or swallowing, pain in the arms, back, chest, neck, or
jaw, slow or difficult speech, dizziness or fainting,
weakness, numbness, or inability to move an arm or leg, bone pain, painful, frequent, or difficult
urination, blood in urine, extreme thirst, weakness, dry mouth, nausea, vomiting, breath that
smells fruity, decreased consciousness, sudden headache,
blurred vision, vision changes, difficulty moving eyes, drooping eyelids, confusion, seizures.
Ref: medline plus
• Goserelin Implant
Side effects: In men hot flashes, sexual dysfunction, decreased erections and lower urinary tract
symptoms are common.
In women dysfunctional uterine bleeding or endometriosis and included (>20%): hot flushes,
headache, sweating, acne, emotional lability, depression, decreased libido, vaginitis, breast
atrophy, seborrhea, and peripheral edema are noticed.
Tumor flare can occur on the initiation of Goserelin for both men and women being treated for
cancer.
Ref: [Link]
• Triptorelin:
Side Effects:
Headache, heartburn, constipation, hot flashes (a sudden wave of mild or intense body heat),
sweating, or clamminess, decreased sexual ability or desire, mood changes such as crying,
irritability, impatience, anger, and aggression, leg or joint pain, breast pain, depression, pain,
itching, swelling, or redness at the place where injection was given, difficulty falling asleep or
staying asleep, cough.
Contraindications:
Triptorelin is classified as Pregnancy Category X and contraindicated in pregnant women or in
women who may become pregnant. Hormonal changes caused by triptorelin increase the risk for
pregnancy loss. Studies done on pregnant rats demonstrated maternal toxicity and embryo-fetal
toxicities.

• LHRH Agonist:
• Degarelix
Side effects:
More common
o Back pain
o blurred vision
o dizziness
o fever
o flushing or redness of the skin
o hard lump
o headache
o nervousness
o pain
o pounding in the ears
o slow or fast heartbeat
o small lumps under the skin
o swelling
o unusually warm skin
Less common
o Bladder pain
o bloody or cloudy urine
o chills
o decrease in testicle size
o decreased interest in sexual intercourse
o difficult, burning, or painful urination
o difficulty in moving
o frequent urge to urinate
o inability to have or keep an erection
o increased sweating
o loss in sexual ability, desire, drive, or performance
o lower back or side pain
o muscle pain or stiffness
o pain in the joints
Rare
o Chest pain or discomfort
o fainting
o irregular heartbeat
o pounding heartbeat
ref: [Link]
Contraindication:
o Patients with previous hypersensitivity reactions.
o Pregnancy Category X. Fetal harm can occur when
administered to pregnant women.
Ref: [Link]
• Relugolix:
Side effects:
Less common
o Chest pain or discomfort
o confusion
o difficulty in speaking
o double vision
o headache
o inability to move the arms, legs, or facial muscles
o inability to speak
o nausea
o pain or discomfort in the arms, jaw, back, or neck
o slow speech
o sweating
o vomiting
Rare
o Bleeding gums
o cloudy urine
o coughing up blood
o decreased frequency or amount of urine
o difficult, burning, or painful urination
o difficulty in swallowing
o dizziness
o fainting
o frequent urge to urinate
o increased menstrual flow or vaginal bleeding
o increased thirst
o loss of appetite
o lower back or side pain
o nosebleeds
o paralysis
o prolonged bleeding from cuts
o red or black, tarry stools
o red or dark brown urine
o slow, fast, pounding, or irregular heartbeat
o swelling of the face, fingers, or lower legs
o trouble breathing
o unusual tiredness or weakness
o weight gain
Incidence not known
o Large, hive-like swelling on face, eyelids, lips, tongue, throat, hands, legs, feet, or sex
organs.
Ref: [Link]
Contraindications:
Hypersensitivity reactions, including pharyngeal edema and other serious cases of
angioedema, have been reported in post marketing.
Ref: [Link]
• Treatment of lower androgen levels from other parts of body

• Abiraterone
Side effects:
fatigue, arthalgia, hypertension, nausea, edema, hypokalemia, hot flush, diarrhea, vomiting,
upper respiratory infection, cough, and headache.
Contraindications:
Hypersensitivity to the Abiraterone acetate or to any of the excipients of Abiraterone.
Ref:[Link]

• Ketoconazole
Side effects:
Shampoo: Topical treatment with ketoconazole shampoo 2% is generally well tolerated. As with
other shampoos, a local burning sensation, itching or contact dermatitis (due to irritation or
allergy) may occur on exposed areas. Oily and dry hair have been reported rarely with the use of
ketoconazole shampoo 2%.

Cream: Commonly observed adverse reactions to Ketoconazole cream in clinical trials were skin
application site burning sensation, erythema and pruritus. Uncommon adverse reactions are
application site bleeding, discomfort, dryness, inflammation, irritation, paraesthesia and reaction;
bullous eruption, dermatitis contact, rash, skin exfoliation and sticky skin.

Tablet: Ketoconazole is very well tolerated. Nausea and itching may occasionally occur. In some
patients, an idosyncratic liver reaction may occur (incidence 1:10000). Ref: [Link]
Contraindications:
Hypersensitivity to ketoconazole. (Ref:[Link])
• 1st Gen Anti-androgen:
• Flutamide:
Side Effects:
o Cardiovascular System: hypertension in 1% of patients. Rarely thrombophlebitis,
pulmonary embolism, myocardial infarction.

o Central Nervous System: CNS (drowsiness/confusion/depression/anxiety/nervousness)

reactions occurred in 1% of patients. Rarely insomnia, tiredness, headache, dizziness, weakness,
malaise, blurred vision and decreased libido have been reported.

o Endocrine System: gynecomastia in 9% of patients. Rarely breast tenderness sometimes

accompanied by galactorrhoea.

o Gastrointestinal System: nausea/vomiting occurred in 11%; diarrhea 12%, anorexia 4%,

and other gastrointestinal disorders occurred in 6% of patients. Increased appetite, indigestion
and constipation have also been reported.

o Hematopoietic System: anaemia occurred in 6% of patients, leukopenia 3%,

thrombocytopenia 1%.

o Liver and Biliary System: clinically evident hepatitis and jaundice occurred in <1% of
patients.

o Skin: irritation at the injection site and rash occurred in 3% of patients. Photosensitivity
reactions have been reported in five patients.

Contraindications:
Flutamide tablets are contraindicated in patients who have shown hypersensitivity to flutamide or
any component of this preparation. Flutamide is contraindicated in patients with severe hepatic
impairment. Flutamide has not been studied in women and is not indicated for this population,
particularly for nonserious or non-threatening conditions. Ref:[Link]
• Bicalutamide
Side Effects:
More common
o Bloating or swelling of the face, arms, hands, lower legs, or feet
o blood in the urine
o blurred vision
o body aches or pain
o chills
o congestion
o cough
o cough producing mucus
o difficult or labored breathing
o dizziness
o dryness or soreness of the throat
o fever
o headache
o hoarseness
o lower back or side pain
o nervousness
o painful or difficult urination
o pounding in the ears
o rapid weight gain
o runny nose
o slow or fast heartbeat
o sweating
o tender, swollen glands in the neck
o tightness in the chest
o tingling of the hands or feet
o trouble with swallowing
o unusual weight gain or loss
o voice changes
Less common
o Abnormal growth filled with fluid or semisolid material
o ankle, knee, or great toe joint pain
o arm, back, or jaw pain
o bleeding from the rectum or bloody stools
o blindness
o bloody nose
o burning feeling while urinating
o burning, tingling, numbness, or pain in the hands, arms, feet, or legs
o change in bowel habits
o chest pain, discomfort, tightness or heaviness
o confusion
o decrease in frequency of urination
o decrease in urine volume
o decreased vision
o difficulty in passing urine (dribbling)
o difficulty with swallowing or eating
o dilated neck veins
o dry mouth
o fainting
o irregular breathing or heartbeat
o joint stiffness or swelling
o lightheadedness
o loss of appetite
o lump or swelling in the abdomen or stomach
o nausea
o no blood pressure or pulse
o noisy breathing
o pain or discomfort in the arms, jaw, back, or neck
o painful blisters on the trunk of the body
o persistent, non-healing sore
o rapid, shallow breathing
o reddish patch or irritated area
o sensation of pins and needles
o shiny bump
o stabbing pain
o stomach discomfort
o stopping of the heart
o sunken eyes
o thirst
o tumor
o unconsciousness
o unexplained weight loss
o unusual tiredness or weakness
o vomiting
o weight gain
o white, yellow, or waxy scar-like area
o wrinkled skin
o yellow skin or eyes
Incidence not known
o Bleeding gums
o coughing up blood
o hives or welts, itching, skin rash
o increased menstrual flow or vaginal bleeding
o large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex
organs
o paralysis
o prolonged bleeding from cuts
o red or black, tarry stools
o red or dark brown urine and redness of skin
ref: [Link]
Contraindications:
o Hypersensitivity
o Female patients (esp pregnant-may harm fetus)
Ref: [Link]
• Nilutamide:
More common
o Blood in the urine
o blurred vision
o chest pain
o chills
o cough
o diarrhea
o difficult or labored breathing
o dizziness
o fever or chills
o general feeling of discomfort or illness
o headache
o joint pain
o loss of appetite
o muscle aches and pains
o nausea
o nervousness
o pale skin
o pounding in the ears
o runny nose
o shivering
o shortness of breath
o slow or fast heartbeat
o sneezing
o sore throat
o sweating
o tightness in the chest
o trouble with sleeping
o troubled breathing with exertion
o unusual bleeding or bruising
o unusual tiredness or weakness
o vomiting
o wheezing
Less common
o Arm, back, or jaw pain
o blindness
o bloody, black, or tarry stools
o change in color vision
o decreased urine output
o decreased vision
o difficulty seeing at night
o dilated neck veins
o fainting
o fast or irregular heartbeat
o increased cough
o increased sensitivity of the eyes to sunlight
o irregular breathing
o swelling of the face, fingers, feet, or lower legs
o vomiting of blood or material that looks like coffee grounds
o weight gain or loss
ref:[Link]
Contraindications:
o liver disease or severe breathing problems.
o Nilutamide can cause serious lung problem.
Ref: [Link]
• 2nd Gen Anti Androgen
• Enzalutamide:
Side Effect:
More common
o Back pain
o bloating or swelling of the face, arms, hands, lower legs, or feet
o blood in the urine
o blurred vision
o chest pain
o chills
o cough with mucus
o difficulty with breathing
o dizziness
o fever
o loss of bladder or bowel control
o nervousness
o painful or difficult urination
o pounding in the ears
o slow or fast heartbeat
o sore throat
o tingling of the hands or feet
o unable to move the legs
o unusual weight gain or loss
Less common
o Anxiety
o confusion or excitement
o depression
o fainting
o falling
o lightheadedness
o loss of memory
o memory or attention span problems
o nightmares or vivid dreams
o rapid, shallow breathing
o Rare
o Seizures
o Incidence not known
o Headache
o hives, itching, skin rash
o hoarseness
o irritation
o joint pain, stiffness, or swelling
o redness of the skin
o swelling of the eyelids, face, lips, hands, or feet
o tightness in the chest
o trouble breathing or swallowing
o unusual drowsiness, tiredness, weakness, or feeling of sluggishness
Ref:[Link]
Contraindication:
Not recommended for pregnant woman.
Ref: [Link]
• Apalutamide
Side Effects:
More common
o Bloating or swelling of the face, arms, hands, lower legs, or feet
o blurred vision
o constipation
o depressed mood
o difficulty with moving
o dizziness
o dry skin and hair
o falls
o feeling cold
o hair loss
o headache
o hoarseness or husky voice
o joint pain
o muscle cramp, pain, and stiffness
o nervousness
o pain in the legs
o pounding in the ears
o rapid weight gain
o slow or fast heartbeat
o tingling of the hands or feet
o unusual tiredness or weakness
o unusual weight gain or loss
o weight gain
Less common
o Bloody urine
o chest pain, discomfort, or tightness
o decreased urine output
o dilated neck veins
o irregular breathing or heartbeat
o nausea
o pain in the shoulders, arms, jaw, or neck
o sweating
o trouble breathing
o vomiting
o Incidence not known
o Blistering, peeling, or loosening of the skin
o chills
o cough
o diarrhea
o fever
o general feeling of discomfort or illness
o itching
o joint or muscle pain
o red irritated eyes
o red skin lesions, often with a purple center
o sore throat
o sores, ulcers, or white spots in the mouth or on the lips
o swollen glands
o thickening of bronchial secretions
o unusual bleeding or bruising
Contraindications:
o Not recommended for pregnant women.

• Darolutamide
Side Effect:
More common
o Black, tarry stools
o bleeding gums
o blood in the urine
o bloody nose
o blurred vision
o coughing or spitting up blood
o difficulty in breathing or swallowing
o dizziness
o frequent urination
o headache
o increased menstrual flow or vaginal bleeding
o lower abdominal or stomach cramping
o nausea and vomiting
o nervousness
o nosebleeds
o painful urination
o paralysis
o pounding in the ears
o prolonged bleeding from cuts
o red or dark brown urine
o red or black, tarry stools
o slow, fast, or irregular heartbeat
o vomiting of blood or material that looks like coffee grounds
o unusual bleeding or bruising
Less common
o Blood in the urine
o chest pain or discomfort
o pain in the shoulders, arms, jaw, or neck
o painful or difficult urination
o seizures
o sweating
o trouble breathing
Contraindications:
None

The future of hormone therapy in prostate cancer looks promising, with ongoing research and
advancements aimed at improving patient outcomes. Here are several key perspectives:

• Personalized Medicine: Advances in genetic profiling and biomarkers are likely to enable
more tailored hormone therapy approaches. Understanding an individual’s specific cancer
characteristics can help identify the most effective treatment options.

• Combination Therapies: Combining hormone therapy with other treatments, such as

immunotherapy or targeted therapies, is an area of active research. These combinations may
enhance efficacy and help overcome resistance to standard hormone therapies.

• Novel Hormonal Agents: New hormonal agents, such as second-generation androgen

receptor inhibitors (e.g., enzalutamide, abiraterone), are being developed and tested. These drugs
may provide benefits over traditional therapies, particularly in castration-resistant prostate
cancer.

• Adjuvant and Neoadjuvant Use: The use of hormone therapy in earlier stages of prostate
cancer, either before surgery (neoadjuvant) or after (adjuvant), is being explored to improve
long-term outcomes.
• Management of Side Effects: Future developments may focus on minimizing the side
effects of hormone therapy, improving quality of life for patients. This could include better
supportive care strategies or medications to counteract adverse effects.

• Long-Term Outcomes and Survivorship: Research will continue to focus on the long-
term effects of hormone therapy and the management of late-onset complications, providing
insights into survivorship care.

• Access and Equity: Efforts to ensure equitable access to innovative hormone therapies
across diverse populations will be crucial in improving overall outcomes.

Overall, the integration of new technologies, treatments, and personalized approaches holds great
potential for enhancing hormone therapy in prostate cancer.

Chemotherapy Treatment of Prostate cancer:

Chemotherapy refers to any type of therapy that uses chemicals to kill or halt the growth of
cancer cells. While chemotherapy is unlikely to cure prostate cancer, it may provide some
benefits to patients. For example, it may be used:

• To relieve symptoms associated with very advanced or metastatic disease, improving the
patient’s quality of life.
• To improve the outcome of prostate cancer surgery if administered for a short time after
the procedure.
• To work in conjunction with hormone therapy and improve the patient outcome.
• To prolong the life of a prostate cancer patient who no longer responds to hormone
therapy.
• To treat men with advanced prostate cancer who carry the AR-V7 gene variant.

Side Effects of Chemotherapy:

All chemotherapy drugs work in slightly different ways, making it challenging to predict side
effects for individual patients. Dosages, drug combinations and drug responses will vary from
patient to patient.

The American Cancer Society lists the following as the most common side effects of
chemotherapy:

• Hair loss
• Mouth sores
• Loss of appetite
• Nausea and vomiting
• Diarrhea
• Increased risk of infections (due to reduced white blood cells)
• Easy bruising or bleeding (due to reduced blood platelets)
• Fatigue (due to reduced red blood cells)

Chemo drugs used to treat prostate cancer:

For prostate cancer, chemo drugs are typically used one at a time. Some of the chemo drugs used
to treat prostate cancer include:

Docetaxel
Cabazitaxel
Mitoxantrone
Estramustine
Carboplatin
Docetaxel
Side effects of Docetaxel in Chemotherapy treatment of prostate cancer:
More common:
• Black, tarry stools
• bleeding gums
• blistering, peeling, or loosening of the skin
• blood in the urine or stools
• burning, tingling, numbness, or pain in the hands, arms, feet, or legs
• chest pain or tightness
• chills
• cough
• decrease in the amount of urine
• diarrhea
• difficulty in swallowing
• difficulty moving
• dizziness
• dry eyes
• fainting
• fast, slow, or irregular heartbeat
• fever
• heartburn
• hives, itching, skin rash
• hoarseness
• irritation
• joint pain, stiffness, or swelling
• lower back or side pain
• muscle pain, cramps, or stiffness
• noisy, rattling breathing
• nosebleeds
• pain or burning feeling in the throat
• painful or difficult urination
• pale skin
• pinpoint red spots on the skin
• red skin lesions, often with a purple center
• red, irritated eyes
• redness of the skin
• sensation of pins and needles
• severe lack or loss of strength
• sore throat
• sores, ulcers, or white spots on the lips or tongue or inside the mouth
• stabbing pain
• swelling of the eyelids, face, lips, hands, or feet
• trouble breathing
• unusual bleeding or bruising
• unusual tiredness or weakness
• vomiting
• weight gain
• Less common
• Bluish color of the skin
• blurred vision
• burning or itching of the eyes
• changes in skin color
• chest discomfort
• confusion
• constipation
• discharge, excessive tearing
• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting
position
• lightheadedness
• nausea
• pain or discomfort in the arms, jaw, back, or neck
• pain, tenderness, or swelling of the foot or leg
• rapid, shallow breathing
• redness, pain, or swelling of the eye, eyelid, or inner lining of the eyelid
• severe stomach pain
• sweating
• vomiting of blood or material that looks like coffee grounds
• Rare
• Dilated neck veins
• extreme tiredness or weakness
• fast, pounding, or irregular heartbeat or pulse
• headache
• irregular breathing
• nervousness
• pounding in the ears
• Incidence not known
• Agitation
• dark urine
• decreased awareness or responsiveness
• depression
• drowsiness
• dry mouth
• general feeling of tiredness or weakness
• hostility
• increased thirst
• indigestion
• light-colored stools
• loss of appetite
• loss of consciousness
• mood or mental changes
• muscle spasms (tetany) or twitching seizures
• nausea
• rapid, shallow breathing
• rectal bleeding
• seizures
• severe abdominal pain, cramping, or burning
• severe sleepiness
• stomach cramps, pain, or tenderness
• stomach pain, continuing
• tremor
• unusual drowsiness, dullness, or feeling of sluggishness
• vomiting of material that looks like coffee grounds, severe and continuing
• yellow eyes or skin

Some side effects may occur that usually do not need medical attention. These side effects may
go away during treatment as your body adjusts to the medicine. Also, your health care
professional may be able to tell you about ways to prevent or reduce some of these side effects.
Check with your health care professional if any of the following side effects continue or are
bothersome or if you have any questions about them:

More common:
• Absent, missed, or irregular menstrual periods
• bad, unusual or unpleasant (after)taste
• change in sense of smell
• change in taste
• discoloration of the fingernails or toenails
• dry skin
• loss or thinning of the hair
• stopping of menstrual bleeding
• swelling or inflammation of the mouth
• weight loss
Less common:
• Dry, red, hot, or irritated skin
• Incidence not known
• Hearing loss
• pain and redness of the skin at the place of earlier radiation treatment
Ref:(Mayo Clinic)

Contraindications of Docetaxel in Chemotherapy treatment of prostate cancer:

Absolute contraindications are hypersensitivity reactions and absolute neutrophil count <1500
cells/mm3. Treatment with taxanes is relatively contraindicated in patients with pre-existing lung
conditions, such as chronic obstructive pulmonary disorder. A common complication
accompanying taxane treatment is pulmonary toxicity. Pulmonary complications can be life-
threatening, especially in predisposed patients with compromised lung function, and avoidance is
necessary if possible. Additionally, before administering therapy, patients are screened for renal,
hepatic, and bone marrow function to establish potential drug tolerability and the adverse drug
reactions of treatment.
ref: National Institutes of Health (NIH) (.gov)

Cabazitaxel (Jevtana)
Side effects of Cabazitaxel in Chemotherapy treatment of prostate cancer:
Along with its needed effects, a medicine may cause some unwanted effects. Although not all of
these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur:
More common:
• Black, tarry stools
• bleeding gums
• bloating or swelling of the face, arms, hands, lower legs, or feet
• blood in the urine or stools
• burning, numbness, tingling, or painful sensations
• chest pain or tightness
• chills
• cough
• difficult or labored breathing
• difficult or painful urination
• fever
• lower back or side pain
• pale skin
• pinpoint red spots on the skin
• rapid weight gain
• sore throat
• sores, ulcers, or white spots on the lips or in the mouth
• swollen glands
• unsteadiness or awkwardness
• unusual bleeding or bruising
• unusual tiredness or weakness
• unusual weight gain or loss
• weakness in the arms, hands, legs, or feet
Less common:
• Blurred vision
• confusion
• decreased urination
• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting
position
• dry mouth
• fainting
• fast, slow, or irregular heartbeat
• lightheadedness
• rapid breathing
• sunken eyes
• sweating
• thirst
• wrinkled skin
• Incidence not known
• Blue lips, fingernails, or skin
• burning feeling in the chest or stomach
• fast breathing
• frequent urination
• general feeling of discomfort or illness
• indigestion
• lower abdominal cramping
• nausea
• severe constipation
• stomach pain or upset
• tenderness in the stomach area
• thickening of bronchial secretions
• vomiting
Some side effects may occur that usually do not need medical attention. These side effects may
go away during treatment as your body adjusts to the medicine. Also, your health care
professional may be able to tell you about ways to prevent or reduce some of these side effects.
Check with your health care professional if any of the following side effects continue or are
bothersome or if you have any questions about them:
More common:
• Belching
• change in taste
• constipation
• cracked lips
• decreased weight
• diarrhea
• difficulty with swallowing
• hair loss
• headache
• heartburn
• indigestion
• lack or loss of strength
• loss of appetite
• stomach discomfort
• thinning of the hair
• weight loss
• Less common
• Back pain
• difficulty with moving
• muscle pain, spasm, or stiffness
• pain in the joints
• pain, itching, burning, swelling, or a lump under your skin where the needle is placed
Ref:( Mayo Clinic)

Contraindications of Cabazitaxel in Chemotherapy treatment of prostate cancer:

• The labeling for Cabazitaxel includes a boxed warning regarding the potential for death
from neutropenia. Cabazitaxel should not be administered to patients with neutrophil counts of
1,500/mm3 or below. Dose reductions are recommended following neutropenic fever or
prolonged neutropenia. The administration of growth factor may reduce the risk of complications
resulting from neutropenia, and primary prophylaxis with G–CSF should be considered in high-
risk patients.20 According to the NCCN treatment guidelines, risk factors for complications from
neutropenia include age older than 65 years, poor performance status, a history of neutropenic
fever, extensive prior radiation, and poor nutrition status.37 Secondary prophylaxis with G–CSF
should be considered if febrile neutropenia develops during treatment with cabazitaxel.20

• The boxed warning also mentions the potential for severe hypersensitivity reactions,
including generalized rash or erythema, hypotension, and bronchospasm. If such reactions occur,
treatment should be discontinued immediately and appropriate therapy should be administered.
Cabazitaxel is contraindicated in patients with a history of severe hypersensitivity reactions to
this drug or to other medications that are formulated with polysorbate 80.20

• Additional warnings and precautions include the potential for GI symptoms, such as
nausea, vomiting, and diarrhea, during treatment with Cabazitaxel. Diarrhea may be severe and
may result in dehydration and electrolyte imbalance requiring rehydration and treatment with
antiemetic and antidiarrheal medications. Treatment with Cabazitaxel might need to be delayed,
or the dosage may have to be reduced in patients with severe diarrhea (grade 3 or greater).20

• Renal failure was reported in the pivotal clinical trial of Cabazitaxel. Most cases occurred
in association with dehydration, sepsis, or obstructive uropathy.20
Ref: National Institutes of Health (NIH) (.gov)

Mitoxantrone
Side effects of Mitoxantrone in Chemotherapy treatment of prostate cancer:
This drug can have a number of side effects, and some of them can be serious.

Anyone who is going to start using this drug should have a special visit with the clinician, who
will discuss with them the risks and benefits of the drug, what they can expect, and what their
preferences are.

According to guidelines published in 2018, there is evidence that Mitoxantrone can lead to:

• cardiomyopathy, or diseases of the heart muscle

• ovarian failure
• male infertility
• chromosomal changes
• promyelocytic leukemia
Heart failure:
Mitoxantrone may cause heart failure, which can be life-threatening. This can happen during
therapy or months to years after therapy.

Lowered immunity:
This drug can cause the white blood cell count to go down, indicating reduced immunity. This
increases the chance of having an infection.

A doctor will not normally give this drug if a person’s neutrophil count is less than 1,500, unless
they have acute nonlymphocytic leukemia.

Bleeding problems:
The platelet count may also go down, which increases the chance of bleeding.

Discoloration of urine or eyes:

Mitoxantrone may turn the urine blue-green for a few days after each dose.

It may also make the whites of the eyes a little blue, but this, too, will go away.

Other common side effects:

The most common side effects of Mitoxantrone include:

• nausea
• hair loss
• menstrual problems, including a loss of menstrual periods
• upper respiratory tract infections
• urinary infections
These are not usually serious, and a doctor can treat them.
Ref: (MedicalNewsToday)

Contraindications of Mitoxantrone in Chemotherapy treatment of prostate cancer:

Hypersensitivity to Mitoxantrone or any component of the formulation.
Ref: Pediatric Oncall,
(children health care)

Estramustine
Side effects of Estramustine in Chemotherapy treatment of prostate cancer:
Serious side effects of estramustine:
Along with its needed effects, estramustine may cause some unwanted effects. Although not all
of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking
estramustine:

Rare:
• black, tarry stools
• blood in urine or stools
• cough or hoarseness
• fever or chills
• headaches (severe or sudden)
• loss of coordination (sudden)
• lower back or side pain
• painful or difficult urination
• pains in chest, groin, or leg (especially calf of leg)
• pinpoint red spots on skin
• shortness of breath (sudden, for no apparent reason)
• slurred speech (sudden)
• unusual bleeding or bruising
• vision changes (sudden)
• weakness or numbness in arm or leg
• skin rash or fever
• unusual tiredness or weakness
More common:
• swelling of feet or lower legs
Other side effects of estramustine:
Some side effects of estramustine may occur that usually do not need medical attention. These
side effects may go away during treatment as your body adjusts to the medicine. Also, your
health care professional may be able to tell you about ways to prevent or reduce some of these
side effects.

Check with your health care professional if any of the following side effects continue or are
bothersome or if you have any questions about them:

More common:
• breast tenderness or enlargement
• decreased interest in sex
• diarrhea
• nausea
Less common:
• trouble in sleeping
• Vomiting

Ref: [Link]
Contraindications of Estramustine in Chemotherapy treatment of prostate cancer:
Estramustine is contraindicated in those known to be hypersensitivity to it, estradiol or nitrogen
mustard. It is also contraindicated in patients with active thrombophlebitis or thromboembolic
disorders.
Ref: [Link]

Carboplatin
Side effects of Carboplatin in Chemotherapy treatment of prostate cancer:
Common side effects:
These side effects happen in more than 10 in 100 people (more than 10%). You might have one
or more of them. They include:

Increased risk of getting an infection:

Increased risk of getting an infection is due to a drop in white blood cells. Symptoms include a
change in temperature, aching muscles, headaches, feeling cold and shivery and generally
unwell. You might have other symptoms depending on where the infection is.

Infections can sometimes be life threatening. You should contact your advice line urgently if you
think you have an infection.

Breathlessness and looking pale:

You might be breathless and look pale due to a drop in red blood cells. This is called anemia.

Bruising, bleeding gums and nosebleeds:

This is due to a drop in the number of platelets in your blood. These blood cells help the blood to
clot when we cut ourselves. You may have nosebleeds or bleeding gums after brushing your
teeth. Or you may have lots of tiny red spots or bruises on your arms or legs (known as
petechiae).

Less commonly you might also bleed from other areas of the body. For instance, some people
might notice their poo is quite dark or they might pass fresh blood.
Let your healthcare team know if you have any signs of bleeding.
Feeling or being sick:
Feeling or being sick is usually well controlled with anti-sickness medicines. It might help to
avoid fatty or fried foods, eat small meals and snacks and take regular sips of water. Relaxation
techniques might also help.

It is important to take anti sickness medicines as prescribed even if you don’t feel sick. It is
easier to prevent sickness rather than treat it once it has started.

Changes to how your liver works:

You might have liver changes that are usually mild and unlikely to cause symptoms. They
usually go back to normal when treatment finishes. You have regular blood tests to check for any
changes in the way your liver is working.

Kidney damage:
To help prevent kidney damage, it is important to drink plenty of water. You might also have
fluids into your vein before, during and after treatment. You have blood tests before your
treatments to check how well your kidneys are working.

Tummy (abdominal) cramps and pain:

Tell your treatment team if you have this. They can check the cause and give you medicine to
help.

Low level of minerals in the blood:

Carboplatin can cause low levels of minerals such as sodium, potassium, calcium and
magnesium in your blood. Some minerals are more likely to cause symptoms than others. Low
calcium and magnesium could cause muscle cramping or twitching. In most cases low mineral
levels are picked up on blood tests.

You have regular blood tests during treatment to check this.

Occasional side effects:
These side effects happen in between 1 and 10 out of every 100 people (between 1 and 10%).
You might have one or more of them. They include:

• an allergic reaction that can cause a rash, shortness of breath, redness or swelling of the
face and dizziness. Some allergic reactions can be life threatening. Alert your nurse or doctor if
notice any of these symptoms
• diarrhea
• constipation
• sore mouth and ulcers - use mouthwashes to keep your mouth clean and let your team
know if you need painkillers
• numbness and tingling in arms, hands, legs and feet (peripheral neuropathy). This can
happen soon after starting treatment and usually isn't permanent
• hearing problems - this can be ringing in your ears (tinnitus) or changes to your hearing
• hair loss - this can be either thinning of the hair or complete loss and is not usually
permanent
• loss of taste or changes to how food and drink tastes - your taste should return after
treatment is finished
• changes to your vision including your eyesight getting worse. This is temporary and
should return to normal after treatment
• changes to the way your heart works. Symptoms might include feeling tired, short of
breath and lacking energy. Your doctor will do tests if they are worried you have heart changes
• sore or painful muscles, joints and bones
• problems with passing urine - drink plenty of water and tell your nurse or doctor
• inflammation of the lungs. This can cause shortness of breath and a cough. Let your
healthcare team know straight away if you are finding it difficult to breathe
• wheezing and tightness of the chest
• tiredness and weakness (fatigue)
Other side effects:
The following side effects have also been reported. But it's not clear how often they happen. You
might have one or more of them. They include:
• a stroke. Symptoms can include drooping of one side of the face, being unable to smile,
having numbness or weakness on one side of the body or being unable to talk. Dial 999
immediately if you have these symptoms
• loss of appetite
• blood clots that can be life threatening; signs are pain, redness and swelling where the
clot is. Feeling breathless can be a sign of a blood clot in the lung. Contact your healthcare team
straight away if you have any of these symptoms
• changes to your blood pressure - this can be either high or low
• pain, redness or swelling at the injection site. Tell your nurse straight away as this can
cause damage to the tissue
• not enough fluid in the body (dehydration) - drink plenty of fluids
• inflammation of the pancreas which can cause tummy pain and feeling or being sick
• a rare disorder of the nerves causing headache, confusion and changes of vision, Contact
your healthcare team straight away, this condition is reversible
• a kidney condition that can cause bloody diarrhea, vomiting, fever, bloating, tummy pain
or cramping. Contact your team straight away if you have these symptoms
• developing a second cancer
• a blood disorder where your red blood cells get destroyed faster than they can be made
(hemolytic anemia)
• small blood clots in the blood vessels inside the kidney (hemolytic uremic syndrome).
Symptoms can include bloody diarrhea, weakness, high temperature or being sick
• feeling generally unwell
• changes to the levels of chemicals in your blood due to the breakdown of tumor cells
(tumor lysis syndrome). You have regular blood tests to check for this
Ref: [Link]

Contraindications of Carboplatin in Chemotherapy treatment of prostate cancer:

• Carboplatin Injection is contraindicated in patients with a history of severe allergic
reactions to cisplatin or other platinum-containing compounds.

• Carboplatin Injection should not be employed in patients with severe bone marrow
depression or significant bleeding.
Ref: [Link]
The future of chemotherapy in prostate cancer is evolving, with several promising directions
aimed at improving efficacy and patient outcomes. Here are some key perspectives:

• Enhanced Combination Therapies: Ongoing research is focusing on combining

chemotherapy with newer agents, such as targeted therapies and immunotherapies. These
combinations may improve effectiveness and help overcome resistance.

• Personalized Approaches: Advances in genomic profiling and biomarkers are expected to

guide treatment decisions. Understanding a patient’s specific tumor characteristics will allow for
more tailored chemotherapy regimens.

• Improved Drug Formulations: New delivery methods and formulations (e.g.,

nanoparticle-based therapies) could enhance the effectiveness of existing chemotherapeutic
agents while reducing side effects.

• Exploring Earlier Use: There’s growing interest in using chemotherapy earlier in the
treatment process, especially for aggressive forms of prostate cancer, potentially improving
outcomes when combined with hormone therapy.

• Novel Chemotherapeutic Agents: Research is underway to identify and develop new

chemotherapeutic agents that target prostate cancer more effectively, particularly in cases
resistant to standard treatments.

• Focus on Quality of Life: Future developments will likely prioritize strategies to

minimize the side effects of chemotherapy, enhancing patients' quality of life during treatment.

• Long-term Outcomes Research: Continued investigation into the long-term effects of

chemotherapy on prostate cancer patients will help refine treatment protocols and survivorship
care plans.

• Access and Equity: Efforts to ensure equitable access to innovative chemotherapy options
will be crucial in improving overall care for diverse patient populations.
As research progresses, the role of chemotherapy in prostate cancer treatment is expected to
become more integrated with other modalities, leading to better-targeted and more effective
therapies.

Targeted Therapy in treatment of Prostate Cancer:

Targeted therapy is a type of cancer treatment that uses drugs or other substances to precisely
identify and attack certain types of cancer cells. A targeted therapy can be used by itself or in
combination with other treatments, such as traditional or standard chemotherapy, surgery, or
radiation therapy. If your treatment plan includes targeted therapy, knowing how it works and
what to expect can often help you prepare for treatment and make informed decisions about your
care.

Targeted Therapy Side Effects

Targeted therapy drugs have different side effects than standard or traditional chemotherapy.
Some targeted drugs have very few side effects, and others can cause more or more serious
problems. There are many different types of targeted drugs, and their side effects depend largely
on the type of drug that's given and what it targets and intense itching. An allergic reaction often
includes other serious symptoms such as trouble breathing, dizziness, tightness in the throat or
chest, or swelling of the lips or tongue. If you have these kinds of symptoms, get emergency help
and call your doctor right away.
Skin problems
Many targeted therapy drugs cause a rash or other skin changes. These skin problems usually
develop slowly over days to weeks after your treatment starts. They are not signs of a drug
allergy.
In contrast, allergic reactions are different because they tend to start suddenly, usually within
minutes to hours after taking the drug. They may include hives (raised skin welts that often go
away in a day or so) and intense itching. An allergic reaction often includes other serious
symptoms such as trouble breathing, dizziness, tightness in the throat or chest, or swelling of the
lips or tongue. If you have these kinds of symptoms, get emergency help and call your doctor
right away.
Skin changes are caused by the way some targeted therapy drugs work. For instance, some
targeted drugs attack the epidermal growth factor receptor (EGFR) protein, which tells the cancer
cells to grow and divide. These are called EGFR inhibitors, and examples are cetuximab
(Erbitux), panitumumab (Vectibix), and erlotinib (Tarceva). The problem is that normal skin cells
also have a lot of EGFR, so drugs that target or block EGFR can affect skin cells, too. They turn
off the signal for skin cells to grow normally and make it harder for them to retain moisture.
Drugs called angiogenesis inhibitors often target vascular endothelial growth factor (VEGF)
proteins. Bevacizumab (Avastin) is one of these drugs. The VEGF proteins help tumors build and
keep a blood supply, but they also seem to be important to the very small blood vessels in the
hands and feet. Blocking these proteins leads to damage in these tiny blood vessels which can
cause hand-foot syndrome (described later).

Changes in how your skin feels: Your skin may start to feel like it’s sunburned, before any
redness or rash shows up. Even though it doesn’t look different, the sensation can be disturbing.
You may notice this change on your face as early as the first week of treatment.
Photosensitivity: Your skin will likely become much more sensitive to light and more easily
damaged by UV rays during treatment. It may very easily be burned and blister, even after very
little sun exposure or exposure to sun coming through windows.
Rash: This is the most common skin change from targeted drugs. The risk of getting a rash and
how bad it gets depends on the type and dose of the targeted drug. In most people, the rash is
mild. It often looks like acne and shows up on the scalp, face, neck, chest, and upper back. In
severe cases it can affect other parts of the body.
The rash most often starts as skin redness and swelling. It’s often worst within the first few
weeks of treatment. By about a month into treatment, the skin usually crusts and gets very dry
and red. In the weeks after that, round, flat or raised red spots and pimples with pus in the center
often appear. In some people this can lead to skin infections. The rash can itch, burn, or sting,
and may be painful. It may get better on its own or stay about the same during the rest of
treatment, but it should go away completely about a month after treatment is stopped.
The rash can be very distressing and make a person feel self-conscious around others. There are
some medications that your doctor can try to make you feel better while you have the rash.
Prevention and treatment of rashes are discussed later.
Dry skin: This is very common for many targeted therapy drugs. It can start within the first few
weeks, but nearly everyone getting targeted therapy has dry skin after 6 months of treatment. The
skin can become very dry, brittle, itchy, and scaly and may even crack open – especially on the
hands and feet. Cracking can happen by itself, but it tends to be worse when there’s also a rash.
Itching: Many skin changes, like rash or dryness, can cause itching.
Red, sore cuticles (the areas around the nails): Some targeted drugs can cause swollen, red, and
painful sores around the fingernails and toenails. (This can look a lot like an infection or an
ingrown nail.) This most often happens to the big toes and thumbs. These sores may become
infected. Nails may also become brittle and grow more slowly.
Hand-foot syndrome: Hand-foot syndrome (HFS) has been linked to many cancer treatment
drugs, including some targeted therapies. The cause of this syndrome isn’t known for sure. It
may have to do with damage to the tiny blood vessels in the hands and feet, or with the drugs
themselves leaking out of the blood vessels and causing damage.
HFS usually starts during the first two to six weeks of treatment. Painful sensitivity, tingling, or
numbness in the hands and feet are the earliest symptoms of HFS. Then, the palms of the hands
and the soles of the feet become red and swollen. The redness looks a lot like sunburn and may
blister. In severe cases, the blisters can open up and become sores. The affected skin also can
become dry, peel, and crack.
HFS can be painful and can affect your ability to walk and do your normal activities. If it
becomes severe, pain medicines may be needed. Let your doctor know if you’re having HFS
symptoms – even if they’re mild. Treating HFS early can help keep it from getting worse. Like
the other skin changes, it can be treated, and there are things you can do to try to prevent it.
Changes in hair growth: Some targeted drugs can cause the hair on your head to become thin, dry
and brittle, or even curly. Long-term use may lead to bald patches or complete loss of scalp hair.
Facial hair may grow faster than usual, including longer, thicker, curly eyebrows and eyelashes
that may need to be trimmed. But in some men, facial hair growth slows down. Eyebrows may
thin out as well. These changes usually don’t happen right away, but you may notice them later
as treatment goes on.
Some people notice sores on their scalp and on other hairy areas. Scars caused by these sores
may keep your hair from growing back after treatment.
Changes in hair or skin color: Some targeted drugs can turn the skin or hair a yellowish color
during treatment. In a few people, hair and/or skin gets darker. This tends to go away once
treatment ends.
Changes in and around the eyes: The eyes may burn, and become dry or red. In some people, the
eyelids get red, tender, and swollen, and the lashes may become crusty. Sometimes the eyelids
may turn inward or outward. Distorted eyelids or prolonged dryness can damage the outer part of
the eye (the cornea). Talk with your doctor or nurse about managing these changes to avoid
injury, pain, or infection.
Other common and serious side effects
Some of the other common and serious side effects caused by targeted therapy drugs are listed
here. This is not a complete list, as each targeted drug can have different side effects.
High blood pressure
Some targeted drugs, especially those called angiogenesis inhibitors, can raise your blood
pressure. There isn’t really anything you can do to prevent this, but your doctor will watch your
blood pressure closely if you’re getting a drug that can cause this side effect. Some people need
medicine to bring their blood pressure down to safe levels during treatment. They should stay on
this medicine until their doctor tells them it can be stopped.
Bleeding or blood clotting problems
Some targeted therapy drugs interfere with new blood vessel growth. This can lead to problems
with bruising and bleeding. These problems are not common and do not happen to everyone. But
it can help to be aware of them because there’s no known way to prevent them.
Bleeding, such as from the stomach and intestines, can be severe and even life threatening. Tell
your doctor if you throw up blood or material that looks like coffee grounds, or if you notice dark
or black stools or bright red blood in your stool. These can be signs of bleeding in the stomach or
intestines.
Some drugs can also cause blood clots in the lungs and legs, as well as heart attacks and strokes.
Let your doctor know if you have problems with sudden swelling, pain, or tenderness in the arm
or leg. If you have chest pain, sudden shortness of breath, vision problems, weakness, seizures,
or trouble speaking, get emergency help. These can be symptoms of serious problems caused by
blood clots.
Slow wound healing
By blocking new blood vessel growth, some of these drugs interfere with wound healing. This
can lead to old wounds (cuts) opening up again and new wounds not closing. It can also lead to
holes (called perforations) opening up in the stomach or intestine. Tell your doctor right away if
you have pain in your belly or vomiting.
Because some of these drugs can affect wound healing, they usually need to be stopped before
any planned surgery, including dental procedures. Talk to your cancer doctor as soon as you
know about a planned surgery or other procedure so you can find out what to do.
Heart damage
Some drugs can damage the heart, especially if used with certain chemotherapy drugs. Your
doctor may test your heart function before starting treatment. Possible symptoms of heart
damage might include chest pain, increased coughing, trouble breathing (especially at night),
rapid weight gain, dizziness, fainting, or swelling in the ankles or legs.
Autoimmune reactions
Certain targeted therapy drugs work by basically taking the brakes off the body’s immune
system. This can lead to serious side effects if the immune system starts to attack healthy parts of
the body. In some people this can cause serious reactions in the lungs, intestines, liver, skin, eyes,
nerves, hormone-making glands, or other organs. This isn’t common but in some people it might
be serious enough to be life threatening.
Swelling
Some targeted therapies cause facial swelling, especially around the eyes. They can also cause
swelling in the feet and legs, as well as the hands. This usually doesn’t need to be treated, but a
diuretic (water pill) may be used in severe cases.
Other side effects
Other side effects have also been linked to treatment with some targeted therapy drugs. Many of
these side effects are the same as those seen with standard chemo drugs, and include:
• Nausea and vomiting
• Diarrhea or constipation
• Mouth sores
• Shortness of breath or trouble breathing
• Cough
• Feeling tired all the time (fatigue)
• Headache
• Hair loss
• Damage to organs such as the thyroid gland, liver, or kidneys
• Allergic reactions (while getting an IV drug)
• Increased risks of certain infections
• Second cancers
Your cancer care team will watch you closely during treatment and will check you often. Side
effects can and should be treated as early as possible. It’s important that you tell your cancer care
team about any changes in how you feel or anything you notice that’s new or unusual. Tell them
right away so they can treat any problems and try to keep them from getting worse.

Contraindication of targeted therapy

Anemia, bleeding and low white blood cell countsSome targeted therapies damage bone marrow,
where blood cells are made. This can result in too few red blood cells (anemia), too few platelets
(thrombocytopenia) and a low white blood cell count (neutropenia).
Ref: [Link]
[Link]

Future Perspectives of Target Therapy

• Advances in Precision Medicine:

With the integration of genomics and advanced molecular diagnostics, the future of targeted
therapy is promising. Precision medicine involves tailoring treatments to a patient’s specific
cancer biology, allowing for more effective and less toxic therapies. The use of genomic profiling
can identify mutations or alterations in prostate cancer cells, such as PTEN or BRCA mutations,
allowing doctors to select the most appropriate targeted treatment. This personalized approach
aims to make treatments more effective by matching patients with therapies likely to yield the
best response.
• Emerging Targeted Agents and Biomarkers:
Ongoing research aims to identify new targets within prostate cancer cells, paving the way for
innovative agents that can inhibit cancer growth more precisely. Biomarkers, like circulating
tumor DNA or prostate-specific antigens (PSA), are gaining traction for real-time monitoring of
therapy efficacy. These biomarkers can help track the tumor’s response to therapy and allow
physicians to modify the treatment plan quickly if the cancer develops resistance.

• Combination Therapies and Reduced Resistance:

To prevent or delay the onset of resistance to targeted therapies, research is exploring
combination therapies. Combining targeted agents with traditional therapies or immunotherapies
may yield a more comprehensive approach to treating prostate cancer. For example, pairing
androgen receptor inhibitors with PARP inhibitors has shown promising results in clinical trials.
This strategy not only enhances therapeutic efficacy but also reduces the likelihood of the cancer
adapting and becoming resistant.

• Challenges and Ethical Considerations:

While targeted therapies are revolutionizing prostate cancer treatment, challenges persist,
including high treatment costs and limited accessibility. Precision medicine, which relies heavily
on genetic testing, raises ethical questions regarding patient privacy and data use. Additionally,
while targeted therapy has a high initial effectiveness, the possibility of resistance development
remains a hurdle. Research and policy efforts are underway to address these challenges, aiming
for cost reduction, broader accessibility, and ethical guidelines to protect patient information.

Immunotherapy in Prostate Cancer:

Immunotherapy is treatment that uses your body's own immune system to help fight cancer.
Get information about the different types of immunotherapy and the types of cancer they are
used to treat.
How Immunotherapy Is Used to Treat Cancer
Immunotherapy is treatment that uses certain parts of a person’s immune system to fight
diseases such as cancer. This can be done in a couple of ways:
• Stimulating, or boosting, the natural defenses of your immune system so it works
harder or smarter to find and attack cancer cells
• Making substances in a lab that are just like immune system components and using
them to help restore or improve how your immune system works to find and attack
cancer cells.
In the last few decades, immunotherapy has become an important part of treating some
types of cancer. New immunotherapy treatments are being tested and approved, and new
ways of working with the immune system are being discovered at a very fast pace.
Immunotherapy works better for some types of cancer than for others. It’s used by itself for
some of these cancers, but for others it seems to work better when used with other types of
treatment.
What the immune system does?
Your immune system is a collection of organs, special cells, and substances that help protect
you from infections and some other diseases. Immune cells and the substances they make
travel through your body to protect it from germs that cause infections. They also help
protect you from cancer in some ways.
The immune system keeps track of all of the substances normally found in the body. Any new
substance that the immune system doesn’t recognize raises an alarm, causing the immune
system to attack it. For example, germs contain substances such as certain proteins that are
not normally found in the human body. The immune system sees these as “foreign” and
attacks them. The immune response can destroy anything containing the foreign substance,
such as germs or cancer cells.
The immune system has a tougher time targeting cancer cells, though. This is because cancer
starts when normal, healthy cells become changed or altered and start to grow out of control.
Because cancer cells actually start in normal cells, the immune system doesn’t always
recognize them as foreign.
Clearly there are limits on the immune system’s ability to fight cancer on its own, because
many people with healthy immune systems still develop cancer:
• Sometimes the immune system doesn’t see the cancer cells as foreign because the
cells aren’t different enough from normal cells.
• Sometimes the immune system recognizes the cancer cells, but the response might
not be strong enough to destroy the cancer.
• Cancer cells themselves can also give off substances that keep the immune system
from finding and attacking them.
To overcome this, researchers have found ways to help the immune system recognize cancer
cells and strengthen its response so that it will destroy them. In this way, your own body is
actually getting rid of the cancer, with some help from science.
Types of cancer immunotherapy
There are several main types of immunotherapy used to treat cancer, and many are being
studied. For more information about immunotherapy as a treatment for a specific
cancer, please choose a cancer type.
1. Checkpoint inhibitors: These drugs basically take the ‘brakes’ off the immune system,
which helps it recognize and attack cancer cells.
2. Chimeric antigen receptor (CAR) T-cell therapy: This therapy takes some T-cells from
a patient's blood, mixes them with a special virus that makes the T-cells learn how to
attach to tumor cells, and then gives the cells back to the patient so they can find,
attach to, and kill the cancer.
3. Cytokines: This treatment uses cytokines (small proteins that carry messages between
cells) to stimulate the immune cells to attack cancer.
4. Immunomodulators: This group of drugs generally boosts parts of the immune
system to treat certain types of cancer.
5. Cancer vaccines: Vaccines are substances put into the body to start an immune
response against certain diseases. We usually think of them as being given to healthy
people to help prevent infections. But some vaccines can help prevent or treat cancer.
6. Monoclonal antibodies (mAbs or MoAbs): These are man-made versions of immune
system proteins. mAbs can be very useful in treating cancer because they can be
designed to attack a very specific part of a cancer cell.
7. Oncolytic viruses: This treatment uses viruses that have been modified in a lab to
infect and kill certain tumor cells.
8. Monoclonal Antibodies and Their Side
References
1. American Society of Clinical Oncology (ASCO). ASCO Annual
Meeting 2019:
2. Immunotherapy for lung cancer, gastrointestinal cancers and
targeted therapy for breast
3. cancer. Accessed at [Link]. Content is no longer available.
4. American Society of Clinical Oncology (ASCO). Understanding
5. immunotherapy. Accessed at [Link]. Content is no longer
available.
6. Bayer VR, Davis ME, Gordan RA, et al. Immunotherapy. In
Olsen MM, LeFebvre KB,
7. Brassil KJ, eds. Chemotherapy and Immunotherapy Guidelines
and Recommendations
8. for Practice. Pittsburgh, PA: Oncology Nursing Society;
2019:149-189.
9. Brodsky AN. Cancer immunotherapy: The year in review and a
look at the year ahead.
10. Cancer Research Institute. Accessed at
[Link]
11. 2019/cancer-immunotherapy-2018-review-2019-predict on
December 19, 2019.
12. Coventry BJ. Therapeutic vaccination immunomodulation:
Forming the basis of all
13. cancer immunotherapy. Ther Adv Vaccines Immunother. 2019;
1:7:2515135519862234.
14. Accessed at
[Link] on
December 19,
15. 2019.
16. DeMaria PJ, Bilusic M. Cancer vaccines. Hematol Oncol Clin
North Am. 2019;
17. 33(2):199-214

Monoclonal Antibodies and Their Side Effects

One way the immune system protects the body from germs and
other foreign
substances is by making large numbers of antibodies. An
antibody is a protein that
sticks to a specific protein called an antigen. Antibodies circulate
throughout the body
until they find and attach to the antigen. Once attached, they can
help other parts of the
immune system to destroy the cells containing the antigen.
Researchers can design antibodies that specifically target a
certain antigen, such as
one found on cancer cells. They can then make many copies of
that antibody in the lab.
These are known as monoclonal antibodies (mAbs or Moabs).

★What mAbs are made of

★Types of mAbs used to treat cancer

★Possible side effects of monoclonal antibodies
Monoclonal antibodies are used to treat many diseases, including some types of
cancer. To make a monoclonal antibody, researchers first have to identify the right
antigen to attack. Finding the right antigens for cancer cells is not always easy, and so
far mAbs have proven to be more useful against some cancers than others.
NOTE: Some monoclonal antibodies used to treat cancer are sometimes considered to
be a type of targeted therapy1 because they work by attaching to a specific target on a
cancer cell and stopping it from functioning. But other monoclonal antibodies act like
immunotherapy because they help the immune system find and attack cancer cells.
more effectively immunotherapy because they help the immune system find and attack
cancer cells.
What mAbs are made of
Monoclonal antibodies are man-made proteins that act like human
antibodies in the immune system. There are 4 different ways they can be
made and are named based on what they are made of.
Murine: These are made from mouse proteins, and the names of the
treatments end in -omab.
Chimeric: These proteins are a combination of part mouse and part
human, and the names of the treatments end in -ximab.
Humanized: These are made from small parts of mouse proteins attached
to human proteins, and the names of the treatments end in -zumab
Human: These are fully human proteins, and the names of the treatments
end in – umab.
Types of mAbsused to treat cancer
Naked monoclonal antibodies
Naked mAbs are antibodies that have no drug or radioactive material
attached to [Link] work by themselves. These are the most common
type of mAbs used to treat cancer. Most naked mAbs attach to antigens on
cancer cells, but some work by binding to antigens on other, non
cancerous cells, or even free-floating proteins. Naked mAbs can work in
different ways.
.Some boost a person’s immune response against cancer cells by
attaching to them and acting as a marker for the body’s immune system to
destroy them. An example is rituximab (Rituxan), which is used to treat
some types of non-Hodgkin lymphoma (NHL) and other
cancers.Rituxi20mab binds to the CD antigen, which is found on
cells called B lymphocytes (which include some types of lymphoma cells).
Once attached, the antibody attracts immune cells to destroy these cells.
●Some naked mAbs boost the immune response by targeting immune
system checkpoints.
●Other naked mAbs work mainly by attaching to and blocking proteins on
cancer cells (or other nearby cells) that help cancer cells grow or spread.
For example,trastuzumab (Herceptin) is an antibody against the HER2
protein. Breast and stomach cancer cells sometimes have large amounts
of this protein on their surface, which helps these cells grow. Trastuzumab
binds to these proteins and stops them from becoming active.
Conjugated monoclonal antibodies
Conjugated mAbs are connected to a chemotherapy drug or a radioactive
particle. These mAbs are used as a homing device to take one of these
substances directly to the cancer cells. The mAb circulates throughout the
body until it can find and hook onto the target antigen. It then delivers the
toxic substance where it is needed most. Conjugated mAbs are also
sometimes referred to as tagged, labeled, or loaded antibodies.
Antibody-drug conjugates (ADCs): These mAbs have powerful
chemotherapy (or other) drugs attached to them. Examples include:
●Brentuximab vedotin (Adcetris), an ADC made up of an antibody that
targets the CD30 antigen (found on lymphocytes), attached to a chemo
drug called MMAE
●Ado-trastuzumab emtansine (Kadcyla, also called TDM-1), an ADC made
up of an antibody that targets the HER2 protein, attached to a chemo drug
called DM1
Radiolabeled antibodies: Radiolabeled antibodies have small radioactive
particles attached to them. The antibody delivers radioactivity directly to
cancer cells. Treatment with this type of antibody is sometimes known as
radioimmunotherapy (RIT). The drug and radiation are delivered directly to
the target cells because the mAb looks for the target, and then the
radiation affects the target and nearby cells to a certain extent.
Bispecific monoclonal antibodies
These drugs are made up of parts of 2 different mAbs, meaning they can
attach to 2 different proteins at the same time.
Bispecific T-cell engagers (BiTEs): In these drugs, one part attaches to a
protein on cancer cells, and the other sticks to a protein on immune cells
called T cells. This brings the immune cells into contact with the cancer
cells, which helps the immune system mount a more effective response
against them. BiTEs are becoming an important part of treatment for some
types of cancer.
Possible side effects of monoclonal antibodies
Monoclonal antibodies are given intravenously (injected into a vein). The
antibodies themselves are proteins, and giving them can sometimes cause
an infusion reaction which is something like an allergic reaction. This is
more common while the drug is first
being given. Possible symptoms can include:
●Fever
●Chills
●Weakness
●Headache
●Nausea
●Vomiting
●Diarrhea
●Low blood pressure
●Rashes
Compared with chemotherapy drugs, naked mAbs tend to have fewer
serious side effects. But they can still cause problems in some
people. Some mAbs can have side effects that are related to the antigens
they target. For
example:
●Bevacizumab (Avastin) is an mAb that targets a protein called VEGF that
affects tumor blood vessel growth. It can cause side effects such as high
blood pressure, bleeding, poor wound healing, blood clots, and kidney
damage.
●Cetuximab (Erbitux) is an antibody that targets a cell protein called EGFR,
which is found on normal skin cells (as well as some types of cancer cells).
This drug can cause serious rashes in some people.
References
Acrotech Biopharma. What is Zevalin? Accessed at
[Link] on
December 19, 2019
American Society of Clinical Oncology (ASCO). ASCO Annual Meeting
2019:
Immunotherapy for lung cancer, gastrointestinal cancers and targeted
therapy for breast
cancer. Accessed at [Link]. Content is no longer available.
American Society of Clinical Oncology (ASCO). Understanding
immunotherapy. Accessed at [Link]. Content is no longer available.
Bayer VR, Davis ME, Gordan RA, et al. Immunotherapy. In Olsen MM,
LeFebvre KB,
Brassil KJ, eds. Chemotherapy and Immunotherapy Guidelines and
Recommendations
for Practice. Pittsburgh, PA: Oncology Nursing Society; 2019:149-189.
Bousquet E, Zarbo A, Tournier E, et al. Development of papulopustular
rosacea during
nivolumab therapy for metastatic cancer. Act Derm Venereol. 2017;
97(4):539—540.
Hong D, Sloane DE. Hypersensitivity to monoclonal antibodies used for
cancer and
inflammatory or connective tissue disease. Ann Allergy Asthma Immunol.
2019;
123(1):35-41.
Kaunitz GJ, Loss M, Rizvi et al. Cutaneous eruptions in patients receiving
immune
checkpoint blockade: Clinicopathologic analysis of the nonlichenoid
histologic pattern.
Am J Surg Pathol. 2017; 41(10):1381-1389.
National Cancer Institute (NCI). Immunotherapy to treat cancer. Accessed
at
[Link] on
December 19,2019
CAR T-cell Therapy and Its Side Effects
Your immune system works by keeping track of all the substances normally
found in your body. Any new substance the immune system doesn't
recognize raises an alarm, causing the immune system to attack it
.How CAR T-cell therapy works
.Getting CAR T-cell therapy
●Approved CAR T-cell therapies
●Possible CAR T-cell therapy side effects
Chimeric antigen receptor (CAR) T-cell therapy is a way to get immune
cells called T cells(a type of white blood cell)to fight cancer by changing
them in the lab so they can find and destroy cancer cells. CAR T-cell
therapy is also sometimes talked about as a type of cell-based gene
therapy, because it involves altering the genes inside T cells to help them
attack the cancer.
This type of treatment can be very helpful in treating some types of cancer,
even when other treatments are no longer working.
How CAR T-cell therapy works
Immune receptors and foreign antigens
The immune system recognizes foreign substances in the body by finding
proteins called antigens on the surface of those cells. Immune cells called
T cells have their own proteins called receptors that attach to foreign
antigens and help trigger other parts of the immune system to destroy the
foreign substance.
The relationship between antigens and immune receptors is like a lock and
key. Just as a lock can only be opened with the right key, each foreign
antigen has a unique immune receptor that is able to bind to it.
Cancer cells also have antigens, but if your immune cells don't have the
right receptors, they can't attach to the antigens and help destroy the
cancer cells.
Chimeric antigen receptors (CARs)
In CAR T-cell therapies, T cells are taken from the patient's blood and are
changed in the lab by adding a gene for a receptor (called a chimeric
antigen receptor or CAR), which helps the T cells attach to a specific cancer
cell antigen. The CAR T cells are then given back to the patient.
Since different cancers have different antigens, each CAR is made for a
specific cancer's antigen. For example, in certain kinds of leukemia or
lymphoma, the cancer cells have an antigen called CD19. The CAR T-cell
therapies to treat these cancers are made to attach to the CD19 antigen
and will not work for a cancer that does not have the CD19 antigen.
Getting CAR T-cell therapy
The process for CAR T-cell therapy can take several weeks.
Collecting the T cells
First, white blood cells (which include T cells) are removed from the
patient’s blood using a procedure called leukapheresis. During this
procedure, patients usually lie in bed or sit in a reclining chair. Two IV lines
are needed because blood is removed through one line, the white blood
cells are separated out, and then the blood is put back into the body
through the other line. Sometimes a special type of IV line called a central
venous catheter1 is used, which has both IV lines built in.
The patient will need to stay seated or lying down for 2 to 3 hours during the
procedure. Sometimes blood calcium levels can drop during
leukapheresis, which can cause numbness and tingling or muscle spasms.
This can be treated by replacing the calcium, which may be given by mouth
or through an IV.
Making the CAR T cells
After the white cells are removed, the T cells are separated, sent to the lab,
and altered by adding the gene for the specific chimeric antigen receptor
(CAR). This makes them CAR T cells. These cells are then grown and
multiplied in the lab. It can take several weeks to make the large number of
CAR T cells needed for this therapy.
Receiving the CAR T-cell infusion
Once enough CAR T cells have been made, they will be given back to the
patient. A few days before the CAR T-cell infusion, the patient might be
given chemotherapy2 to help lower the number of other immune cells. This
gives the CAR T cells a better chance to get activated to fight the cancer.
This chemotherapy is usually not very strong because CAR T cells work
best when there are still some cancer cells to attack. Once the CAR T cells
start binding with cancer cells, they start to increase in number and can
help destroy even more cancer cells.
Approved CAR T-cell therapies
CAR T-cell therapies are approved by the US Food and Drug Administration
(FDA) to treat some kinds of lymphomas and leukemias, as well as multiple
myeloma. CAR T-cell therapy is typically used after other types of
treatment have been tried.
Examples of CAR T-cell therapies currently approved include:
●Tisagenlecleucel, also known as tisa-cel (Kymriah)
●Axicabtagene ciloleucel, also known as axi-cel (Yescarta)
●Brexucabtagene autoleucel, also known as brexu-cel (Tecartus)
●Lisocabtagene maraleucel, also known as liso-cel (Breyanzi)
●Idecabtagene vicleucel, also known as ide-cel (Abecma)
●Ciltacabtegene autoleucel, also known as cilta-cel (Carvykti)
Many other CAR T-cell therapies (and similar types of treatment) are now
being studied in clinical trials, in the hope of treating other types of cancer
as well.
Possible CAR T-cell therapy side effects
CAR T-cell therapy can be very effective against some types of hard-to
treat cancers, but it can also sometimes cause serious or even life
threatening side effects. Because of this, it needs to be given in a medical
center that is specially trained in its use, and patients need to be watched
closely for several weeks after getting the CAR T cells.
Cytokine release syndrome (CRS): As CAR T cells multiply, they can
release large amounts of chemicals called cytokines into the blood, which
can ramp up the immunesystem. Serious side effects from this release can
include:
●High fever and chills
●Trouble breathing
●Severe nausea, vomiting, and/or diarrhea
●Feeling dizzy or lightheaded
●Headaches
●Fast heartbeat
●Feeling very tired
●Muscle and/or joint pain
As doctors are gaining more experience with CAR T-cell therapy, they are
learning how to recognize CRS early, as well as how to treat [Link]
system problems: This treatment can sometimes have serious effects on
the nervous system, which can result in symptoms such as:
●Headaches Changes in consciousness
●Confusion or agitation
●Seizures
●Shaking or twitching (tremors)
●Trouble speaking and understanding
●Loss of balance
Because of the risk of these side effects, adult patients are typically
advised not to drive, operate heavy machinery, or do any other potentially
dangerous activities for at least several weeks after getting treatment.
Other serious side effects:
Other possible serious side effects of CAR T-cell therapy can include:
●Allergic reactions during the infusion
●Abnormal levels of minerals in the blood, such as low potassium,
sodium, or phosphorous levels
●A weakened immune system, with an increased risk of serious infections
●Low blood cell counts, which can increase the risk of infections, fatigue,
and bruising or bleeding
If you are getting CAR T-cell therapy, it’s very important to report any side
effects to your health care team right away, as there are often medicines
that can help treat them.
References
American Society of Clinical Oncology (ASCO). ASCO Annual Meeting
2019:
Immunotherapy for lung cancer, gastrointestinal cancers and targeted
therapy for breast
cancer. Accessed at [Link]. Content is no longer available.
American Society of Clinical Oncology
(ASCO). Understanding immunotherapy. Accessed at [Link]. Content
is no longer
available.
Bayer VR, Davis ME, Gordan RA, et al. Immunotherapy. In Olsen MM,
LeFebvre KB,
Brassil KJ, eds. Chemotherapy and Immunotherapy Guidelines and
Recommendations
for Practice. Pittsburgh, PA: Oncology Nursing Society; 2019:149-189.
National Cancer Institute (NCI). (NCI). CAR T cells: Engineering patients’
immune cells
to treat their cancers. Accessed at
[Link] on
December 19, 2019.
Porter DL, Maloney DG. Cytokine release syndrome (CRS). Up-to-date. 2021.
Accessed
at [Link] on
April 01,2021
Immune Checkpoint Inhibitors and Their
Side Effects
_____________________________________________________________________
An important part of the immune system is its ability to tell between normal
cells in the body and those it sees as “foreign” (such as germs and cancer
cells). This allows the immune system to attack the foreign cells while
leaving normal cells alone.
Part of how the immune system does this is by using “checkpoint” proteins
on immune cells. The checkpoints act like switches that need to be turned
on (or off) to start an immune response. But cancer cells sometimes find
ways to use these checkpoints to avoid being attacked by the immune
system.
●PD-1 and PD-L1 inhibitors
●CTLA-4 inhibitors
●LAG-3 inhibitors
●Side effects of checkpoint inhibitors
Medicines known as monoclonal antibodies can be designed to target
these checkpoint proteins. These drugs are called immune checkpoint
inhibitors Checkpoint inhibitors don't kill cancer cells directly. They work
by helping the immune system to better find and attack the cancer cells,
wherever they are in the body.
Medicines that target different checkpoint proteins are now used to treat
many types of cancer.
All of these drugs can be given as an infusion into a vein (IV). Some of them
can now be given as an injection under the skin (subcutaneously) over
several minutes as well.
PD-1 and PD-L1 inhibitors
PD-1 is a checkpoint protein on immune cells called T cells. It normally
acts as a type of “off switch” that helps keep the T cells from attacking
other cells in the body. It does this when it attaches to PD-L1, a protein on
some normal (and cancer) cells. When PD-1 binds to PD-L1, it basically
tells the T cell to leave the other cell alone. Some cancer cells have large
amounts of PD-L1, which helps them hide from an immune attack.
Monoclonal antibodies that target either PD-1 or PD-L1 can block this
binding and boost the immune response against cancer cells.
PD-1 inhibitors
Examples of drugs that target PD-1 include:
●Pembrolizumab (Keytruda)
●Nivolumab (Opdivo)
●Cemiplimab (Libations)
PD-L1 inhibitors
Examples of drugs that target PD-L1 include:
●Atezolizumab (Tecentriq and Tecentriq Hybreza)
●Avelumab (Bavencio)
●Durvalumab (Imfinzi)
Both PD-1 and PD-L1 inhibitors have been shown to be helpful in treating
many different types of cancer.
CTLA-4 inhibitors
CTLA-4 is another checkpoint protein on some T cells that acts as a type of
“off switch”to help keep the immune system in check.
Ipilimumab (Yervoy) and tremelimumab (Imjuno) are monoclonal
antibodies that attach to CTLA-4 and stop it from working. This can help
boost the body’s immune response against cancer cells.
These drugs are typically used along with a PD-1 or PD-L1 inhibitor. These
combinations can be used to treat several types of cancer.
LAG-3 inhibitors
LAG-3 is a checkpoint protein on some types of immune cells that normally
acts as a type of “off switch” to help keep the immune system in check.
Relatlimab is a monoclonal antibody that attaches to LAG-3 and stops it
from working. This can help boost the body’s immune response against
cancer cells.
This drug is given along with the PD-1 inhibitor nivolumab (in a combination
known as Opdualag). It can be used to treat melanoma of the skin, and it’s
being studied for use in several other types of cancer.
Side effects of checkpoint inhibitors
Some of the more common side effects of checkpoint inhibitors include:
●Diarrhea
●Fatigue
●Cough
●Nausea
●Skin rash
●Poor appetite
●Constipation
●Muscle and joint pain
Other, more serious side effects occur less often:
Infusion reactions: Some people might have an infusion reaction while
getting these drugs. This is like an allergic reaction, and can include fever,
chills, flushing of the face, rash, itchy skin, feeling dizzy, wheezing, and
trouble breathing. It’s important to tell your doctor or nurse right away if
you have any of these symptoms while getting one of these drugs.
Autoimmune reactions: By targeting a checkpoint protein, these drugs
remove one of the safeguards on the body's immune system. Sometimes
the immune system responds by attacking other parts of the body, which
can cause serious or even life-threatening problems in the lungs,
intestines, liver, hormone-making glands, kidneys, or other organs.
It’s very important to report any new side effects to someone on your
health care tea mas soon as possible. If serious side effects do occur,
treatment may need to be stopped and you might be given high doses of
corticosteroids to suppress your immune system.
References
American Society of Clinical Oncology (ASCO). ASCO Annual Meeting
2019:
Immunotherapy for lung cancer, gastrointestinal cancers and targeted
therapy for breast
cancer. Accessed at [Link]. Content is no longer available.
American Society of Clinical Oncology
(ASCO). Understanding immunotherapy. Accessed at [Link]. Content
is no longer
available.
Bayer VR, Davis ME, Gordan RA, et al. Immunotherapy. In Olsen MM,
LeFebvre KB,
Brassil KJ, eds. Chemotherapy and Immunotherapy Guidelines and
Recommendations
for Practice. Pittsburgh, PA: Oncology Nursing Society; 2019:149-189.
Kaunitz GJ, Loss M, Rizvi et al. Cutaneous eruptions in patients receiving
immune
checkpoint blockade: Clinicopathologic analysis of the nonlichenoid
histologic pattern.
Am J Surg Pathol. 2017; 41(10):1381-1389.
Cancer Vaccines and Their Side Effects
Most of us know about vaccines given to healthy people to help prevent
infections, such as measles and chicken pox. These vaccines use
weakened or killed germs like viruses or bacteria to start an immune
response in the body. Getting the immune system ready to defend against
these germs helps keep people from getting infections.
●Vaccines to help prevent cancer
●Vaccines to treat cancer
●Other vaccines
Most vaccines used to treat cancer work the same way, but they make the
person’s immune system attack cancer cells. The goal is to help treat cancer
or to help keep it from coming back after other treatments. But there are also
some vaccines that may actually help prevent certain cancers.
Vaccines to help prevent cancer
Some cancers are caused by viruses. Vaccines that help protect against
infections with these viruses might also help prevent some of these cancers.
●Some strains of the human papillomavirus (HPV)1 have been linked to
cervical, anal, throat, vaginal, vulvar, and penile cancers. In fact, most cervical
cancers are caused by infection with HPV. Vaccinating children and certain
young adults against HPV helps protect against cervical cancer and the other
5 cancers HPV can cause. Read more in Protect Against HPV2.
●People who have chronic (long-term) infections with the hepatitis B virus
(HBV) are at higher risk for liver cancer3. Getting the vaccine to help prevent
HBV infection may lower some people’s risk of getting liver cancer.
These are traditional preventive vaccines that target the viruses that can
cause certain cancers. They may help protect against some cancers, but they
don’t target cancer cell directly because cancer cells have not yet been
formed or found.
These types of vaccines are only useful for cancers known to be caused by
infections. But most cancers, including colorectal, lung, prostate, and breast
cancers, are not thought to be caused by infections.
Vaccines to treat cancer
Cancer treatment vaccines are different from the vaccines that work against
viruses. These vaccines try to get the immune system to mount an attack
against cancer cells in the body. Instead of preventing disease, they are meant
to get the immune system to attack a disease that already exists.
Some cancer treatment vaccines are made up of cancer cells, parts of cells,
or pure antigens (certain proteins on the cancer cells). Sometimes a patient’s
own immune cells are removed and exposed to these substances in the lab to
create the vaccine. Once the vaccine is ready, it’s injected into the body to
increase the immune response against cancer cells.
Vaccines are often combined with other substances or cells called adjuvants
that help boost the immune response even further.
Cancer vaccines cause the immune system to attack cells with one or more
specific antigens. Because the immune system has special cells for memory,
it’s hoped that the vaccine might continue to work long after it’s given.
Sipuleucel-T (Provenge):This drug is used to treat advanced prostate cancer
that is no longer being helped by hormone therapy. Side effects4 are usually
mild and can include fever, chills, fatigue, back and joint pain, nausea, and
headache. A few men may have more severe symptoms, including problems
breathing and high blood pressure.
●Talimogene laherparepvec (T-VEC): This vaccine is approved to treat
advanced melanoma skin cancer. It is made from a herpes virus that has been
altered in the lab to produce a substance that the body normally produces,
called a cytokine. This cytokine boosts the immune system and can cause flu
like symptoms for a short time.
●Other vaccines
Other types of cancer vaccines have shown some promise in clinical trials,
but they are not yet approved in the U.S. to treat cancer.
References
American Society of Clinical Oncology (ASCO). ASCO Annual Meeting 2019:
Immunotherapy for lung cancer, gastrointestinal cancers and targeted therapy
for breast
cancer. Accessed at [Link]. Content is no longer available.
American Society of Clinical Oncology
(ASCO). Understanding immunotherapy. Accessed at [Link]. Content is
no longer
available.
Bayer VR, Davis ME, Gordan RA, et al. Immunotherapy. In Olsen MM, LeFebvre
KB,
Brassil KJ, eds. Chemotherapy and Immunotherapy Guidelines and
Recommendations
for Practice. Pittsburgh, PA: Oncology Nursing Society; 2019:149-189.
Coventry BJ. Therapeutic vaccination immunomodulation: Forming the basis
of all
cancer immunotherapy. Ther Adv Vaccines Immunother. 2019;
1:7:2515135519862234.
Accessed at [Link] on
December 19,
2019.
DeMaria PJ, Bilusic M. Cancer vaccines. Hematol Oncol Clin North Am. 2019;
33(2):199-214.
Saslow D, Andrews KS, Manassaram-Baptiste D, et al. Human papillomavirus
vaccination 2020 guideline update: American Cancer Society guideline
adaptation. CA
Cancer J Clin. 2020; DOI: 10.3322/caac.21616.
Cytokines and Their Side Effects
Cytokines are small proteins that are crucial in controlling the growth and
activity of other immune system cells and blood cells. When released, they
signal the immune system to do its job. Cytokines affect the growth of all
blood cells and other cells that help the body's immune and inflammation
responses. They also help to boost anticancer activity by sending signals that
can help make abnormal cells die and normal cells live longer.
●Interleukins
●Interferons
One specific type of cytokine is called a chemokine. A chemokine can make
immune cells move toward a target. There are different kinds of chemokines,
including interleukins, interferons, tumor necrosis factors, and growth factors.
Some cytokines can be made in a lab and are used to treat cancer. Some are
used to help prevent or manage chemotherapy side effects. They are injected,
either under the skin, into a muscle, or into a vein. The most common ones are
interleukins andvinterferons.
Interleukins
Interleukins are a group of cytokines that act as chemical signals between
white blood cells. Interleukin-2 (IL-2) helps immune system cells grow and
divide more quickly. A man-made version of IL-2 is approved to treat advanced
kidney cancer1 and metastatic melanoma2. IL-2 can be used as a single drug
treatment for these cancers, or it can be combined with chemotherapy or with
other cytokines such as interferon-alfa.
Side effects3 of IL-2 can include flu-like symptoms such as chills, fever,
fatigue, and confusion. Some have nausea, vomiting, or diarrhea. Many
people develop low blood pressure, which can be treated with other
medicines. Rare but potentially serious side effects include an abnormal
heartbeat, chest pain, and other heart problems. Because of these possible
side effects, if IL-2 is given in high doses, it must be done in a hospital.
Other interleukins, such as IL-7, IL-12, and IL-21, continue to be studied for
use against cancer too, both as adjuvants and as stand-alone agents.
Interferons
Interferons are chemicals that help the body resist virus infections and
cancers. The types of interferon (IFN) are named after the first 3 letters of the
Greek alphabet:
●IFN-alfa
●IFN-beta
●IFN-gamma
Only IFN-alfais used to treat cancer. It boosts the ability of certain immune
cells to attack cancer cells. It may also slow the growth of cancer cells
directly, as well as the blood vessels that tumors need to grow.
IFN-alfa can be used to treat these cancers:
●Hairy cell leukemia
●Chronic myelogenous leukemia (CML)
●Follicular non-Hodgkin lymphoma
●Cutaneous (skin) T-cell lymphoma
●Kidney cancer
●Melanoma
●Kaposi sarcoma
Side effects of interferons can include:
●Flu-like symptoms (chills, fever, headache, fatigue, loss of
appetite, nausea,
vomiting)
●Low white blood cell counts (which increase the risk of infection)
●Skin rashes
●Thinning hair
These side effects can be severe and can make treatment with
interferon hard for many people to tolerate. Most side effects don’t
last long after the treatment stops, but fatigue can last longer. Other
rare long-term effects include damage to nerves, including those in
the brain and spinal cord.
References
American Society of Clinical Oncology (ASCO). ASCO Annual
Meeting 2019:
Immunotherapy for lung cancer, gastrointestinal cancers and
targeted therapy for breast
cancer. Accessed at [Link]. Content is no longer available.
American Society of Clinical Oncology (ASCO). Understanding
immunotherapy. Accessed at [Link]. Content is no longer
available.
Bayer VR, Davis ME, Gordan RA, et al. Immunotherapy. In Olsen MM,
LeFebvre KB,
Brassil KJ, eds. Chemotherapy and Immunotherapy Guidelines and
Recommendations
for Practice. Pittsburgh, PA: Oncology Nursing Society; 2019:149
189.
Brodsky AN. Cancer immunotherapy: The year in review and a look
at the year ahead.
Cancer Research Institute. Accessed at
[Link]
2019/cancer-immunotherapy-2018-review-2019-predict on
December 19, 2019.
Hafeez U, Gan HK, Scott AM. Monoclonal antibodies as
immunomodulatory therapy
against cancer and autoimmune diseases. Curr Opin Pharmacol.
2018; 41:114-121.
Wraith DC. The future of immunotherapy: A 20-year perspective.
Front Immunol.
2017:8:1668. Accessed at
[Link] on
December 19, 2019.
Immunomodulators and
Their Side Effects
Immunomodulators are a group of drugs that mainly target the
pathways that treat multiple myeloma and a few other cancers. They
have many ways to work, including working on the immune system
directly by turning down some proteins and turning up
others.
●Thalidomide, lenalidomide, and pomalidomide
●Bacillus Calmette-Guérin
●Imiquimod
Thalidomide, lenalidomide, and pomalidomide
Thalidomide (Thalomid), lenalidomide (Revlimid), and
pomalidomide (Pomalyst) are known as immunomodulating drugs
(or IMiDs).
These drugs can cause side effects such as drowsiness, fatigue,
constipation, low blood cell counts, and neuropathy (painful nerve
damage). There is also an increased risk of serious blood clots (that
start in the leg and can travel to the lungs). These tend to be more
likely with thalidomide than with the other drugs.
These drugs can also cause severe birth defects if taken during
pregnancy.
Bacillus Calmette-Guérin
Bacillus Calmette-Guérin(BCG) is a germ that doesn’t cause serious
disease in humans, but it does infect human tissues and helps
activate the immune system. This makes BCG useful as a form of
cancer immunotherapy. BCG was one of the earliest
immunotherapies used against cancer and is still being used today.
BCG is used to treat early stage bladder cancer. It is a liquid put into
the bladder through a catheter. BCG attracts the body’s immune
system cells to the bladder, where they can attack the bladder
cancer cells. Treatment with BCG can cause symptoms that are like
having the flu, such as fever, chills, and fatigue. It can also cause a
burning feeling in the bladder. BCG can also be used to treat some
melanoma skin cancers by injecting it directly into the tumors. It's
also used as a vaccine against tuberculosis.
Imiquimod
Imiquimod is a drug that is applied to the skin as a cream. It
stimulates a local immune response against skin cancer cells. It is
used to treat some very early stage skin cancers (or pre-cancers),
especially if they are in sensitive areas such as on the face.
The cream is applied anywhere from once a day to twice a week for
several months. Some people have serious skin reactions to this
drug.
Immunotherapy Safety
Much is known about the need to protect others from exposure to
traditional or standard chemotherapy1 because it is hazardous. This
is why there are safety rules and recommendations for people who
handle chemo drugs. However, because immunotherapy drugs are
newer, there is not as much information about long-term effects of
exposure.
To be safe, many experts recommend treating immunotherapy drugs
as hazardous and taking the same precautions. This is especially
true when immunotherapy drugs are given to treat cancer in
combination with other drugs that are known to be hazardous,so
your cancer care team will take precautions to protect themselves
and others from exposure to them.
●Precautions the cancer care team might take
●Special precautions when taking oral or topical immunotherapy
●Keeping family and friends safe
Precautions the cancer care team might take
You may notice special clothing and protective equipment being
worn by the nurses and other members of your cancer care team.
Pharmacists and nurses who prepare drugs to treat cancer use a
special type of pharmacy that must meet certain regulations. If you
are being cared for in a treatment center, the nurses and others who
give treatment and help take care of patients afterwards wear
protective clothing, such as 2 pairs of special gloves and a gown,
and sometimes goggles or a face shield. If you're getting
immunotherapy through an IV, there might be a disposable pad
under the infusion tubing to protect the surface of the bed or chair.
Special precautions when taking oral or topical immunotherapy
Oral immunotherapy that you take by mouth and swallow, or topical
immunotherapy that you rub on your skin, is usually taken at home.
Some are considered hazardous. There might be special
precautions for storing and handling an immunotherapy drug. You
might be told to be careful not to let others come into contact with it
or your body fluids while taking it and for a time after taking it.
Sometimes you need to wear gloves when touching the pills or
capsules. Some drugs have to be kept in the bottle or box they
came in. And some drugs and the packages they come in need to be
disposed of in a certain way. Some might have to be taken back to
the drug store to be thrown away safely. If you are taking an oral
drug, talk to your cancer care team about whether special
precautions are needed at home.
Keeping family and friends safe
Unless your health care team tells you differently, you can usually be
around family and friends during the weeks and months you're
getting immunotherapy. If you're getting treatment at a center, family
and friends can often come with you. However, some treatment
centers only allow patients in the infusion area and visitors may
need to stay in the waiting room.
You are the only person who should be exposed to the drug you are
getting, but any spilled IV drug, and any powder or dust from a pill or
capsule, or any liquid from oral or topical immunotherapy might be
hazardous to others if they are around it.
It's important to talk to your cancer care team and be aware of
any special precautions that might be needed while you are
taking an immunotherapy drug
References
Brown VT. Targeted therapy. In Olsen MM, LeFebvre KB, Brassil KJ,
eds. Chemotherapy and Immunotherapy Guidelines and
Recommendations for
Practice. Pittsburgh, PA: Oncology Nursing Society; 2019:103-139.

The future of immunotherapy in prostate cancer is quite promising, with ongoing research and
innovations aimed at enhancing its effectiveness. Here are several key perspectives:

• Personalized Immunotherapy: Advances in genomic and biomarker research are paving

the way for personalized immunotherapy approaches. Tailoring treatments based on individual
tumor characteristics and immune profiles can improve outcomes.

• Combination Therapies: Combining immunotherapy with other treatments, such as

hormone therapy, chemotherapy, or targeted therapies, is a focus of ongoing research. These
combinations may enhance the immune response and overcome resistance.

• Checkpoint Inhibitors: While checkpoint inhibitors have shown limited efficacy in

prostate cancer compared to other cancers, ongoing trials are exploring their use in combination
with other agents to boost immune responses.
• Cancer Vaccines: Developments in therapeutic vaccines, such as sipuleucel-T, are being
explored further. Future research may yield more effective vaccine candidates that better
stimulate the immune system against prostate cancer.

• Adoptive Cell Transfer: Techniques like CAR-T cell therapy are being investigated for
prostate cancer. Engineering T cells to target specific tumor antigens may provide a novel
treatment approach.

• Microbiome and Immunotherapy: Research into the role of the microbiome in

modulating immune responses is emerging. Understanding how the microbiome affects
immunotherapy outcomes could lead to novel interventions.
• Enhanced Biomarker Discovery: Identifying reliable biomarkers for predicting
response to immunotherapy will be crucial. This can help select patients who are most likely to
benefit from these treatments.

• Long-Term Effects and Survivorship: Continued research into the long-term outcomes
of immunotherapy, including potential late-onset effects and management strategies, is essential
for improving survivorship care.

• Equity in Access: Ensuring equitable access to innovative immunotherapy options is

vital to improve overall outcomes across diverse patient populations.

Overall, the integration of immunotherapy into the prostate cancer treatment landscape is
expected to grow, offering new avenues for managing the disease, particularly in advanced and
resistant cases.

Bisphosphonates Therapy
Bisphosphonates are a group of medicines used to treat osteopenia or osteoporosis, which are
conditions associated with thin or fragile bones that are at increased risk for fracture. The
medications help strengthen the bones and prevent future bone fractures. Patients with low bone
density or a history of low-energy trauma fractures are recommended to take these medications.
Disorders such as Paget’s disease and cancer that have spread (metastasized) to the bone are
other indications for use. Patients on long-term oral steroid medications may also be
recommended to take these medications.

There are two main types of bisphosphonates — oral (taken by mouth) bisphosphonates and IV
(intravenous, or through your vein) bisphosphonates.
Oral bisphosphonates that healthcare providers in the United States can currently prescribe
include:
• Alendronate (Fosamax®).
• Risedronate (Actonel®).
• Ibandronate (Boniva®). This medication also comes in IV form.
IV bisphosphonates that providers can currently prescribe in the U.S. include:
• Pamidronate (Aredia®).
• Zoledronic acid (Reclast®, Zometa®).
Ref: [Link]

Side Effects of Alendronate(Fosamax)

These are just a few of the more common side effects reported by people who took Fosamax in
clinical trials:
• abdominal pain
• acid reflux
• diarrhea
• constipation*
• indigestion*

Mild side effects of Fosamax

Mild side effects can occur with Fosamax use. This list doesn’t include all possible mild side
effects of the drug. For more information, you can refer to Fosamax’s prescribing information.
Mild side effects that have been reported with Fosamax include:
• abdominal pain
• acid reflux
• diarrhea
• muscle pain
• nausea
• bone pain
• constipation
• indigestion
• mild allergic reaction
Serious side effects of Fosamax
Fosamax may cause serious side effects. In most cases, serious side effects from Fosamax are
rare, but they can occur. The list below may not include all possible serious side effects of the
drug. For more information, you can refer to Fosamax’s prescribing information.
If you develop serious side effects while taking Fosamax, call your doctor right away. If the side
effects seem life threatening or you think you’re having a medical emergency, immediately call
911 or your local emergency number.
Serious side effects that have been reported and their symptoms include:
• Low blood calcium levels. Symptoms can include:
o muscle spasms
o confusion
o tingling of the hands or feet
• Femur bone fractures. Symptoms can include:
o severe pain in the top of your leg
o swelling of the leg
o difficulty walking
• Esophagus or stomach irritation. Symptoms can include:
o difficulty swallowing
o heartburn
o stomach or esophagus ulcers
• Severe joint or muscle pain.
• Severe bone pain*
• Jaw osteonecrosis*
• Severe allergic reaction.

Contraindications of fosamax
• Problems with your esophagus. ...
• Trouble sitting upright or standing. ...
• Hypocalcemia (low calcium level). ...
• Inflammation or ulcers in your digestive system. ...
• Risk of jaw and dental problems. ...
• Kidney problems. ...
• Pregnancy. ...
• Breastfeeding.
Ref: [Link]
Side effects of risedronate
These common side effects of risedronate happen in more than 1 in 100 people. There are things
you can do to help cope with them:

1. Constipation
2. Diarrhoea
3. Indigestion, bloating, stomach pain or wind
4. Feeling sick (nausea)
5. Headaches
6. Mild muscle, bone or joint pain

Serious side effects

Some people may have serious side effects when taking risedronate.
Tell a doctor or call 111 straight away if you have:
• heartburn (or heartburn that gets worse), or problems or pain when swallowing – these
may be signs of ulcers in your food pipe. If this happens, stop taking risedronate and speak to a
doctor
• a loose tooth, mouth sores, or swelling or pain in your mouth or jaw – contact your
dentist as well as your doctor, as this could be a sign of damage to your jawbone
• pain, weakness or discomfort in your thigh, hip or groin – this happens rarely but may be
an early sign of a broken thigh bone
• severe pain in the joints, muscles or bones
• ear pain, discharge from your ear or an ear infection – these can be signs of damage to the
bones in your inner ear
• black or red poo – these can be signs of an ulcer or bleeding from your gut
• blurred vision, light sensitivity, or painful or red eyes – these can be signs of swelling of
the eye
• muscle cramps or spasms, a tingling sensation in your fingers or around your mouth –
these can be symptoms of low calcium levels in your blood

Long-term side effects

For a very small number of people, taking risedronate for more than 2 years can increase their
chances of getting a rare type of bone damage in their inner ear and certain types of breaks to
their thigh bones.
If risedronate is working for you long term, your doctor will look at the benefits and risks of your
treatment after 5 years. They may do some tests to check the strength (density) of your bones.
Then they'll advise you if you should keep taking it.
The benefits of taking risedronate generally outweigh the risks. If you're concerned or have any
questions, talk to your doctor or pharmacist.

Contraindications of Risedronate
Contraindications/Precautions Warnings Risedronate is contraindicated in patients who have
hypocalcemia, a known hypersensitivity to any of its components, or an inability to stand or sit
upright for at least 30 minutes.

Ref: [Link]

Side effects of ibandronate (Boniva)

The most common side effects of ibandronate are listed below. Tell your healthcare provider if
you have any of these side effects that bother you.
• Back pain
• Joint or muscle pain (see below)
• Pain in your arms or legs
• Stomach pain, diarrhea, or indigestion
• Headache
• Flu-like symptoms
Serious Side Effect Of Ibandronate (Boniva)
While less common, the most serious side effects of ibandronate are described below, along with
what to do if they happen.
Esophagus Problems. Taking ibandronate by mouth may irritate the esophagus or upper part of
your gastrointestinal (GI) tract. This irritation can be worse in people who already have stomach
or esophagus problems. In some cases, it can lead to problems such as ulcers, bleeding, or tears
in the esophagus, which may require hospitalization. To reduce the risk of these problems, it is
important to take an ibandronate tablet with a full glass of plain water and stay upright after
taking it. Stop taking ibandronate and call your healthcare provider right away if you have any of
the following symptoms.
• Trouble or pain while swallowing
• Chest pain
• New or worsening heartburn
Low Calcium Level (Hypocalcemia). Ibandronate can cause low calcium levels, also known as
hypocalcemia, which can be serious. Decreased calcium levels can cause a rare dangerous heart
rhythm problem called QT prolongation and torsade de pointes. Some people have a higher risk
of this, including people who are older, have other people in their family who have had these
conditions, have low potassium or magnesium, or who take some medicines for other heart
rhythm problems. Call your healthcare provider if you have any of the following symptoms.
• Changes in your heart rate or rhythm, such as fast or skipping heartbeat
• Fainting
• Numbness, tingling, or burning sensation in your arms, feet, or face (paresthesia)
• Muscle pain, spasms, twitching, or cramps
• Seizures
Severe Pain in the Bones, Joints, or Muscles. Ibandronate may cause severe pain in the bones,
joints, or muscles (musculoskeletal pain). The pain can be severe enough that it could be difficult
to carry out normal activities. Call your healthcare provider if you experience severe pain while
on ibandronate.
Severe Jawbone Problems (Osteonecrosis). Ibandronate can rarely cause severe jawbone
problems, also called osteonecrosis of the jaw. In this condition, your jawbone may get damaged
due to reduced blood flow. You may be at higher risk if you are undergoing certain dental
procedures (such as a tooth extraction or dental implants), if you have poor oral health, or if you
have cancer or certain other conditions. You may be told to see a dentist before starting
ibandronate and to practice good mouth care. Call your healthcare provider right away if you
experience any of the following symptoms of jaw osteonecrosis.
• Jaw pain or discomfort
• Mouth sores
• Loose teeth
Unusual Thigh Bone Fractures. Ibandronate may cause an increased risk for fractures in your
thigh bone, even with a light force. Call your healthcare provider if you experience new or
unusual pain in your thigh, hip, or groin.
Kidney Damage. Kidney damage can happen when using the injectable form of ibandronate. Call
your healthcare provider right away if you have any of the following symptoms of kidney
damage.
• Reduced need to pee
• Swelling in your feet, ankles, or legs (edema)
• Weakness or unusual tiredness
• Difficulty in catching your breath or chest pain/pressure
• Confusion
• Nausea
• Seizures

Contraindications of ibandronate (Boniva)

Ibandronate can cause low calcium levels, also known as hypocalcemia. It should not be used if
you have low blood calcium levels. Kidney Problems. Ibandronate should not be taken if your
kidneys are not working as well as they should be
Ref: [Link]

Side effects of pamidronate (Aredia)

• allergic reactions (skin rash, itching or hives; swelling of the face, lips, or tongue)
• bleeding (bloody or black, tarry stools; red or dark brown urine; spitting up blood or
brown material that looks like coffee grounds; red spots on the skin; unusual bruising or bleeding
from the eyes, gums, or nose)
• bone pain
• increased thirst
• infection (fever, chills, cough, sore throat, pain or trouble passing urine)
• jaw pain, especially after dental work
• joint pain
• kidney injury (trouble passing urine or change in the amount of urine)
• low calcium levels (fast heartbeat; muscle cramps or pain; pain, tingling, or numbness in
the hands or feet; seizures)
• low magnesium levels (fast, irregular heartbeat; muscle cramp or pain; muscle weakness;
tremors; seizures)
• low potassium levels (trouble breathing; chest pain; dizziness; fast, irregular heartbeat;
feeling faint or lightheaded, falls; muscle cramps or pain)
• muscle pain
• pain, redness, or irritation at site where injected
• redness, blistering, peeling, or loosening of the skin, including inside the mouth
• severe diarrhea
• unusual sweating
Side effects that usually do not require medical attention (report to your doctor or health care
provider if they continue or are bothersome):
• constipation
• eye irritation, itching, or pain
• fever
• headache
• increase in blood pressure
• loss of appetite
• nausea
• stomach pain
• unusually weak or tired
• vomiting
Contraindications of pamidronate (Aredia)
Tell your healthcare provider if you have any of the following. Low calcium levels
(hypocalcemia) Kidney problems Poor oral health or dental problems (including use of dentures)
Past thyroid surgery Cancer Blood disorders Pregnancy. It is not known if or how pamidronate
could affect pregnancy or harm an unborn baby.

Ref: [Link]

Side effects of zoledronic acid (Reclast Zometa)

• allergic reactions (skin rash, itching or hives; swelling of the face, lips, or tongue)
• bone pain
• infection (fever, chills, cough, sore throat, pain or trouble passing urine)
• jaw pain, especially after dental work
• joint pain
• kidney injury (trouble passing urine or change in the amount of urine)
• low calcium levels (fast heartbeat; muscle cramps or pain; pain, tingling, or numbness in
the hands or feet; seizures)
• low red blood cell counts (trouble breathing; feeling faint; lightheaded, falls; unusually
weak or tired)
• muscle pain
• palpitations
• redness, blistering, peeling, or loosening of the skin, including inside the mouth
Side effects that usually do not require medical attention (report to your doctor or health care
provider if they continue or are bothersome):
• diarrhea
• eye irritation, itching, or pain
• fever
• general ill feeling or flu-like symptoms
• headache
• increase in blood pressure
• nausea
• pain, redness, or irritation at site where injected

• stomach pain
• upset stomach
Contraindications of zoledronic acid (Reclast Zometa)
Hypocalcemia, acute kidney injury, or CrCl less than or equal to 35 mL/min are
contraindications for use in benign bone disease. [38] In treating hypercalcemia of malignancy,
zoledronate should be avoided in patients with serum creatinine greater than 4.5 mg/dL.
Ref: [Link]
osteoporosis

The future of bisphosphonate therapy in prostate cancer, particularly in managing bone-related

complications, shows several promising directions. Here are some key perspectives:

• Bone Health Management: Bisphosphonates are primarily used to prevent skeletal-

related events in patients with metastatic prostate cancer. Future research may further clarify
their role in bone health maintenance and pain management.

• Combination Treatments: There is potential for combining bisphosphonates with other

therapies, such as hormone therapy or targeted agents, to enhance overall treatment efficacy and
manage bone health better.

• Novel Bisphosphonates: Ongoing research may lead to the development of new

bisphosphonates with improved efficacy and reduced side effects. These could offer better
options for patients with advanced disease.

• Sequential Therapy: Investigating the timing and sequencing of bisphosphonate therapy

with other treatments may optimize patient outcomes, particularly in the context of early
intervention.
• Long-term Effects and Safety: Continued research into the long-term effects and safety
profiles of bisphosphonate therapy will be essential, particularly concerning osteonecrosis of the
jaw and other potential complications.

• Patient-Specific Factors: Future studies may focus on identifying patient-specific

factors that predict response to bisphosphonate therapy, allowing for more personalized treatment
approaches.

• Role in Non-Metastatic Disease: There is potential for exploring bisphosphonate

therapy in non-metastatic prostate cancer settings, particularly in high-risk patients to prevent
future complications.

• Education and Awareness: Increasing awareness among healthcare providers and

patients regarding the benefits and risks of bisphosphonate therapy will be crucial for optimizing
its use.

Overall, as research continues, bisphosphonate therapy is likely to remain an important

component of managing bone health in prostate cancer patients, especially those with advanced
disease. The integration of new findings and therapies will help enhance treatment strategies.