Pharmacotherapy of Prostate Cancer

PST 06106

Basic Pharmacotherapy

Session 32: Pharmacotherapy of Prostate Cancer

Learning Tasks

By the end of this session students are expected to be able to:

Define prostate cancer

Explain pathophysiology of prostate cancer

Explain the clinical presentation of prostate cancer

Outline diagnosis of prostate cancer

Describe pharmacological treatment of prostate cancer

Describe the monitoring of prostate cancer therapy

Definition of Prostate Cancer

Prostate cancer is a malignant neoplasm that arises from the prostate gland.

Prostate cancer has an indolent course; localized prostate cancer is curable by surgery

or

radiation

therapy, but advanced prostate cancer is not yet curable.

The most common type of prostate cancer is adenocarcinoma (95 %)

Tumors

are stratified by T stage, Gleason score (GS), and PSA into three prognostic groups of low, intermediate and high risk.

Definition of Prostate Cancer

Cont

…

Patient can be offered appropriate treatment options according to stage of disease, prognostic risk group and estimated survival taking into account performance status and comorbidity.

Activity: Buzzing

What is the pathophysiology of prostate cancer?

Pathophysiology of Prostate Cancer

The prostate gland is a part of the male reproductive system that helps to make and store seminal fluid.

Because of its location, prostate disease often affects urination, ejaculation, and rarely defecation.

Prostate cancer begins when normal

semen screening

prostate gland cells mutate into cancer cells.

The region of prostate gland where the adenocarcinoma is most common is the peripheral zone.

Pathophysiology of Prostate

Cancer

Cont

…

Initially, small clumps of cancer cells remain confined to otherwise normal prostate glands, a condition known as carcinoma in situ or prostate intraepithelial neoplasia(PIN).

Overtime, these cancer cells begin to multiply and spread to the surrounding prostate tissue (the stroma) forming a tumor.

Eventually

, the tumor may grow large enough to invade nearby organs such as the seminal vesicles, or the rectum, or the tumor cells may develop the ability to travel in the blood stream and lymphatic system.

The invasion of other organs is called metastasis.

Prostate cancer most commonly metastasizes to the bones, lymph nodes, and may invade rectum, bladder and lower ureters after local progression.

Clinical presentation and Diagnosis of Prostate Cancer

Localized Disease

Asymptomatic

Locally Invasive Disease

Impotence

Prostatic symptoms are associated with advanced stages of the disease, which include: reduced potency, urinary frequency and nocturnal, poor stream, hesitancy and terminal

dribbling

Clinical presentation and Diagnosis of Prostate

Cancer Cont.….

Advanced Disease

Back pain

Cord compression

Lower extremity edema

Anemia

Weight loss

Very often patients may present with bone pain including backache or pathological

fracture

Diagnostic and Staging Workup for prostate Cancer

Activity

: Small Group Discussion

What are the drugs treatments for prostate cancer?

Pharmacological Treatment of Prostate Cancer

Luteinizing Hormone–Releasing Hormone Agonists

LHRH agonists are a reversible method of androgen ablation and are as effective

as orchiectomy

.

Leuprolide acetate, leuprolide depot, leuprolide implant,

triptorelin

depot,

triptorelin

implant, and

goserelin

acetate implant are currently available.

Dosing intervals range from once monthly to every 16 weeks.

Leuprolide implant is a

miniosmotic

pump that delivers daily doses for 1 year.

The most common adverse effects of LHRH agonists include disease flare-up during the first week of therapy (

eg

, increased bone pain or urinary symptoms), hot flashes, erectile impotence, decreased libido, and injection-site reactions.

Pharmacological Treatment of Prostate

Cancer

Cont

….

Luteinizing Hormone–Releasing Hormone Agonists…..

Use

of an antiandrogen (

eg

,

flutamide

,

bicalutamide

, or

nilutamide

) prior to initiation of LHRH therapy and for 2 to 4 weeks after is a strategy to minimize initial tumor flare.

Decreases in bone mineral density complicate androgen deprivation therapy (ADT), resulting in increased risk of osteoporosis, osteopenia, and skeletal fractures.

Calcium and vitamin D supplements and a baseline bone mineral density are recommended.

Pharmacological Treatment of Prostate Cancer

Cont

….

Gonadotropin-Releasing Hormone Antagonists

Degarelix binds reversibly to GnRH receptors in the pituitary gland, reducing the production of testosterone to castrate levels in 7 days or less

A major advantage of

degarelix

over LHRH agonists the lack of tumor flares.

Degarelix is administered as a subcutaneous injection every 28 days

Injection site reactions are the most frequently reported adverse effects and include pain, erythema, swelling, induration, and nodules

.

Pharmacological Treatment of Prostate Cancer

Cont

….

Antiandrogens

Monotherapy with

flutamide

,

bicalutamide

, and

nilutamide

is no longer

recommended

due

to decreased efficacy as compared with patients treated with LHRH agonist therapy

Antiandrogens are indicated for advanced prostate cancer only when

combined with an LHRH agonist (

flutamide

and

bicalutamide

]) or

orchiectomy

(

nilutamide

). In combination, antiandrogens can reduce the LHRH

agonist–

inducedflare

.

Enzalutamide is approved as a single agent in metastatic hormone-resistant

prostate

cancer

patients who have previously received docetaxel

.

Pharmacological Treatment of Prostate Cancer

Cont

….

Chemotherapy

It is mainly reserved for hormonal-refractory prostate cancer. The most common adverse events include nausea, alopecia, and myelosuppression.

Cabazitaxel

Neutropenia, febrile neutropenia, neuropathy, and diarrhea are the most significant toxicities.

For Bone metastases/osteolytic/

tumour

induced hypercalcemia:

Zolendronic

acid IV 4mg over 15min given 4 Weekly

Monitoring Of Prostate Cancer Therapy

Monitor primary tumor size, involved lymph nodes, and tumor marker response such as PSA with definitive, curative therapy

PSA level is checked every 6 months for the first 5 years, then annually.

With metastatic disease, clinical benefit can be documented by evaluating performance status, weight, quality of life, analgesic requirements, and PSA or DRE at 3-month intervals

.

Monitoring of Prostate Cancer Therapy

Monitor

primary tumor size, involved lymph nodes, and tumor marker response such as PSA with definitive, curative therapy

PSA level is checked every 6 months for the first 5 years, then annually.

With metastatic disease, clinical benefit can be documented by evaluating performance status, weight, quality of life, analgesic requirements, and PSA or DRE at 3-month intervals.

Key Points

Prostate

cancer is a malignant neoplasm that arises from the prostate gland. Prostate

cancer has an indolent course; localized prostate cancer is curable by surgery or

radiation therapy, but advanced prostate cancer is not yet curable

There are different stages of Prostate Cancer according to

Glearson

score

Metastatic spread can occur by local extension, lymphatic drainage, or

hematogenous

dissemination

Key

Points

Cont

…

The diagnosis is based on various diagnostic criteria and various diagnostic tests such as

abdominal and pelvic USS and or CT Scan, Pelvic MRI in early stage

disease , Bone

scan

etc

The

common drugs used for the treatment of Prostate Cancer are LHRH agonists and

GnRH

antagonists

Monitoring therapy should be done by checking primary tumor size, involved lymph nodes, and tumor marker response such as PSA with definitive, curative therapy. PSA level should checked every 6 months for the first 5 years, then annually.

Evaluation

What

is Prostate Cancer?

What is the pathophysiology of Prostate Cancer?

How is Prostate Cancer diagnosed?

What is the first line treatment of Prostate Cancer

References

Wells

BG,

DiPiro

J,

Schwinghammer

T (2013),

Pharmacotherapy Handbook

(6

th

Ed). New York, NY: McGraw-Hill.

DiPiro

JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey ML, (2008):

Pharmacotherapy: A Pathophysiologic Approach

(7

th

ed

): New York, NY: McGraw-Hill.

Katz M D.,

Matthias KR.,

Chisholm-Burns M A.,

Pharmacotherapy(2011)

Principles & Practice Study Guide: A Case-Based Care Plan Approach

:

New York, NY: McGraw-Hill.

Schwinghammer

TL, Koehler JM (2009)

Pharmacotherapy Casebook: A Patient-Focused Approach

(7

th

ed

): New York, NY: McGraw-Hill.

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