Treatment of Prostate Cancer

Question 1

Androgen Receptor Blockers Drugs:

Answer 1

Bicalutamide
Enzalutamide
Flutamide
Nilutamide

Question 2

GnRH Agonist Drugs:

Answer 2

Goserelin
Histrelin
Leuprolide
Triptorelin

Question 3

17-alpha Inhibitor Drugs:

Answer 3

Abiraterone

Question 4

Immunotherapy Drugs:

Answer 4

Sipuleucel-T

Question 5

Targeted Alkylator Drugs:

Answer 5

Estramustine

Question 6

GnRH Antagonist Drugs:

Answer 6

Degarelix

Question 7

Prostate Cancer the most?

Answer 7

Hormone sensitive of all cancers

Question 8

Prostate Cancer any hormonal therapeutic strategy must take into account?

Answer 8

The two almost equivalent sources of androgens acting in the prostate which include Testicular testosterone and locally produced dihydrotestosterone (DHT) derived from dehydroepiandrosterone of adrenal origin.

Question 9

First-line treatment for prostate cancer

Answer 9

Combined androgen blockade—medical or surgical castration plus a pure anti-androgen.

Question 10

Non-drug approaches for prostate cancer include

Answer 10

Watchful waiting or active surveillance, & external beam irradiation of the prostate

Question 11

Brachytherapy =

Answer 11

Implanted I125 titanium coated “seeds” used to treat early stage disease.

Question 12

Hormonally-responsive Prostatic Tumors Mechanism:

Answer 12

Normal GnRH release is pulsatile, but agonist treatment is continuous. Down-regulation of the GnRH receptor on the pituitary gland and ultimately decreased production of FSH and LH. Serum levels of testosterone consequently falls to castrate levels in 2-4 weeks.

Question 13

GnRH Agonists ALL Adverse Effects:

Answer 13

CV effects: edema, HTN; CNS: headache, fatigue, depression; Decreased bone mineral density; spinal compression
Elevated triglycerides; weight gain; DM
Reduced libido; sexual dysfunction; gynecomastia
Rarely hepatotoxicity
Aches & pains
Pregnancy Cat X

Question 14

Leuprolide Adverse Effects:

Answer 14

Rarely MI/HF

Question 15

Histrelin Adverse Effects:

Answer 15

Seizures, suicidal ideation

Question 16

Degarelix Mechanism & Administration:

Answer 16

Reversible GnRH receptor antagonist given by SC
injection
– Reduced LH and FSH secretion
– Castrate testosterone levels within 3 days

Question 17

Degarelix Common adverse effects include:

Answer 17

– Hot sweats, injection site reaction, weight gain
– Hypertension, arthralgia, chills, fatigue, & impotence.
– Elevated hepatic enzyme levels (reversible) & QT
prolongation

Question 18

Estramustine Mechanism:

Answer 18

Binds EBP on prostate CA Inhibits microtubules, promoting dis-assembly & G2/M arrest
Produces DNA strand breakage
Testosterone levels depressed via negative feedback on HP axis

Question 19

Estramustine Administration:

Answer 19

Oral drug; comparable estrogenic effects to estradiol.

Question 20

Estramustine Common AE include:

Answer 20

GI upset, gynecomastia, mastalgia & impotence.
Edema, thromboembolism, MI, PE & stroke occur as a result of the elevated estradiol levels.
Elevated hepatic enzymes and hyperbilirubinemia are also reported

Question 21

Bicalutamide
Blockade
CYP inhibition
Adverse Effects

Answer 21

Prostate > central [Antagonist + some agonist activity]
CYP inhibition 3A4>2C9/19, 2D6
GI toxicity - Hot flashes – Aches & pains, Hepatotoxicity/failure, Increased time to accommodate transition from light to dark
Teratogen

Question 22

Enzalutamide
Blockade
CYP inhibition
Adverse Effects

Answer 22

Prostate & central
None
CNS: dizziness, insomnia, seizures GI toxicity - Hot flashes – Aches & pains, Hepatotoxicity/failure, URTI, Increased time to accommodate transition from light to dark.
Teratogen

Question 23

Flutamide
Blockade
CYP inhibition
Adverse Effects
BBW

Answer 23

Prostate [Antagonist]
None
Blood dyscrasia, GI toxicity - Hot flashes – Aches & pains, Increased time to accommodate transition from light to dark.
BBW: Hepatotoxicity/failure
Teratogen

Question 24

Nilutamide
Blockade
CYP inhibition
Adverse Effects
BBW:

Answer 24

Prostate & central
None
HF/HTN, Blood dyscrasia, GI toxicity - Hot flashes – Aches & pains, Hepatotoxicity/failure, Increased time to accommodate transition from light to dark.
BBW: Interstitial pneumonitis; respiratory insufficiency

Question 25

Sipuleucel-T Mechanism:

Answer 25

Autologous cellular immunotherapy designed to stimulate T-cell immunity against prostatic acid phosphatase (PAP).

Question 26

Sipuleucel-T Preparation:

Answer 26

– Patient APCs (leukapheresis) cultured with recombinant PAP-GMCSF
– APCs take up antigen, process and express fragments on surface
– Product (with T-, B- & NK-cells) reinfused

Question 27

Sipuleucel-T

Adverse effects

Answer 27

– Mild infusion reactions; fever/chills/dyspnea; GI effects like N/V
– Paresthesias, citrate toxicity & fatigue have all been reported

Question 28

Abiraterone Mechanism:

Answer 28

CYP17 inhibitor (17 α-hydroxylase)
Produces increased mineralocorticoid state

Question 29

Abiraterone Side Effects:

Answer 29

– Hypertension, hypokalemia and fluid retention

– Caution with pre-existing CV issues

Question 30

Abiraterone Adjuvent therapy:

Answer 30

Symptoms prevented/reduced, with corticosteroid to suppress adrenocorticotropic hormone (ACTH) drive
– Adrenocortical insufficiency if withdrawn too quickly

Question 31

Abiraterone Monitor:

Answer 31

• Elevated hepatic enzymes; routine LFTs are required

* Cat. X drug; precautions necessary for female partner