PHARM_prostate cancer

Question 1

name the androgen receptor blockers (3)

Answer 1

bicalutamide
flutamide
nilutamide

AR-B-UTAMIDE

Question 2

name the targeted alkylator used to treat prostate cancer

Answer 2

estramustine

Question 3

name the GnRH agonists (4)

Answer 3

goserelin
histrelin
leuprolide
triptorelin

Question 4

name the GnRH antagonist

Answer 4

degarelix

Question 5

name the 17-alpha inhibitor

Answer 5

abiraterone

Question 6

what is 1st line treatment for prostate cancer?

Answer 6

combined androgen blockade-medical or surgical castration plus a pure anti-androgen

Question 7

how do the GnRH agonists treat prostate cancer?

Answer 7

they cause down regulation of the GnRH receptor on the pituitary gland & ultimately decreased prod. of FSH & LH
-serum levels of testosterone fall at 2-4 wks

Question 8

a gain of function in prostatic cancer in what enzyme can cause a lot of conversion of DHEA –>DHT

Answer 8

3-betahydroxysteroid dehydrogenase

Question 9

what is something you worry about when treating prostate cancer with hormone therapy?

Answer 9

the development of a super androgen receptor that can respond to lower levels or even function as a ligand-independent receptor

Question 10

what is something you worry about when using GnRH agonists when treating prostate cancer?

Answer 10

initial transient dz flare (avoided by 2-4 wks of AR blockers)

Question 11

the GnRH agonists can cause a hypoandrogenic state when given by injection, which includes what kinds of symptoms?

Answer 11

decreased bone mineral density–>spinal compression
elevated triglycerides; weight gain; DM–>CVD
reduced libido; sex dysfunction; gynecomastia–>sexually related

Question 12

how does degarelix work?

Answer 12

reversible GnRH receptor antagonist given by SC injection

• reduced LH & FSH secretion
• reach castrate Testosterone levels w/i 3 days

Question 13

what are some of the AEs of degarelix that are consistent with hypoandrogenic state?

Answer 13

• hot sweats, weight gain

- htn, arthralgia, chills, fatigue, impotence

Question 14

what are some of the AEs of degarelix that are not consistent with a hypoandrogenic state?

Answer 14

QT prolongation & elevated hepatic enzyme levels (reversible)

Question 15

how does estramustine work?

Answer 15

conjugated drug which carries alkylating agent attached to an estradiol structure
-binds Estramustine binding protein (EBP) on prostate CA-inhibits microtubules, promoting dis-assembly & G2/M arrest-produces DNA strand breakage

Question 16

how is estramustine administered?

Answer 16

oral

Question 17

what are some of the common AEs of estramustine?

Answer 17

GI upset, gynecomastia, mastalgia & impotence

Question 18

what may happen with estramustine therapy as a result of the elevated estradiol levels?

Answer 18

edema, thromboembolism, MI, PE or stroke

Question 19

flutamide has a BBW for what?

Answer 19

hepatotoxicity/failure

Question 20

nilutamide has a BBW for what?

Answer 20

respiratory insufficiency

Question 21

all the androgen receptor blockers are teratogens except for what drug?

Answer 21

nilutamide

Question 22

bicalutamide has selectivity for blocking which receptors?

Answer 22

prostate>central

Question 23

flutamide blocks which androgen receptors?

Answer 23

prostate

Question 24

nilutamide blocks which androgen receptors?

Answer 24

prostate & central

Question 25

what type of adverse effects do all the androgen receptor blockers have in common?

Answer 25

all produce AEs of hypoandrogenic state

Question 26

how does sipuleucel-T work?

Answer 26

autologous cellular immunotherapy designed to stimulate T-cell immunity against prostatic acid phosphatase - pt APCs (leukapheresis) cultured w/ recombinant PAP-GM-CSF - APCs take up antigen, process & express fragments on surface - Product (w/ immune cells) reinfused

Question 27

what are some of the AEs of sipuleucel-T?

Answer 27

mild infusion rxns; fever/chills/dyspnea; GI effects like N/V -Paresthesias, citrate toxicity & fatigue

Question 28

how does Abiraterone work?

Answer 28

CYP17 inhibitor (prevents production of androgens)

Question 29

what are some of the AEs of abiraterone?

Answer 29

produces increased mineralocorticoid state - HTN, hypokalemia, & fluid retention - caution w/ pre-existing CV issues

Question 30

how do you reduce the symptoms of an increased mineralocorticoid state with abiraterone?

Answer 30

use corticosteroid to suppress ACTH drive

Question 31

should we use finasteride and dutasteride to prevent prostate cancer?

Answer 31

NO

Question 32

what are the conventional drugs used to treat prostate cancer?

Answer 32

docetaxel and carbazitaxel (poor substrate for P-gp, penetrates BBB) and mitoxantrone (+prednisone) which is used for palliation of severe pain

Question 33

which conventional chemotherapeutic used to treat prostate cancer is a poor substrate for P-gp and penetrates the BBB?

Answer 33

carbazitaxels