PHARM: Prostate Cancer

Question 1

True or false: prostate cancer is the most hormone sensitive of all cancers.

Answer 1

TRUE

Question 2

Which has a longer ligand binding time to androgen receptors, testosterone or DHT?

Answer 2

DHT

Question 3

What is commonly used with GnRH agonists to prevent the disease flare?

Answer 3

androgen receptor antagonists

Question 4

How does prostate cancer evolve into an androgen-insensitive growth pattern?

Answer 4

Changes in AR amplification by point mutation

Changes in expression of AR co-regulatory proteins

Question 5

What is a super androgen receptor?

Answer 5

AR receptor that can respond to lower concentrations of androgens or has the ability to function in a ligand-independent manner.

Question 6

What is the consequence of a gain of stability mutation in 3β-hydroxysteroid dehydrogenase?

Answer 6

can lead to DHT mediated tumor activation (because it governs the conversion of DHEAS to DHT)

Question 7

What were the problems in using estrogens for the treatment of prostate cancer?

Answer 7

when used in oral (high dose) regimens the produced significant adverse effects– primarily those impacting the CV system (DVT, thromboembolism, salt/water retention)

Question 8

How are researchers planning to renew the use of estrogens for the treatment of prostate cancer?

Answer 8

using transdermal estrogens

Question 9

Why are 5-alpha reductase inhibitors not used for prostate cancer?

Answer 9

recent data shows that there is not a benefit from using them

Question 10

What are ER-alpha receptors?

Answer 10

receptors in the prostate that mediate aberrant proliferaiton, inflammation and malignancy when stimulated by estrogen

Question 11

What are ER-beta receptors?

Answer 11

receptors int he glandular epithelium of the prostate that may have a tumor supressive effect (initiate apoptosis via TNF-alpha)

Question 12

What receptor is consistently expressed in androgen-insensitive tumors?

Answer 12

progesterone receptor (but no drug for it)

Question 13

What is first line treatment for prostate cancer?

Answer 13

combined androgen blockage (medical or surgical castration) + pure anti-androgen

Question 14

What is brachytherapy?

Answer 14

non-drug treatment for prostate cancer that includes implanted I125 Titanium coated “seeds”

Question 15

List the androgen receptor blockers?

Answer 15

Bicalutamide
Enzalutamide
Flutamide
Nilutamide

Question 16

Which androgen receptor blocker is a CYP inhibitor?

Answer 16

Bicalutamide

Question 17

Which androgen receptor blocker is specific for prostate AR?

Answer 17

Flutamide

Question 18

Which androgen receptor blocks both central and prostate AR but is better at blocking prostate?

Answer 18

Bicalutamide

Question 19

Which androgen receptor blocker has both antagonist and agonist activity?

Answer 19

Bicalutamide

Question 20

Which androgen receptor blocker is NOT a teratogen?

Answer 20

nilutamide

Question 21

Which androgen receptor blocker can cause male-mediated teratogeniticy?

Answer 21

enzalutamide

Question 22

Which androgen receptor blocker has a BBW for hepatotoxicity and liver failure?

Answer 22

Flutamide

Question 23

Whch androgen receptor blocker has CNS effects like dizziness, insomnia and seizures as well as UTRIs?

Answer 23

Enzalutamide

Question 24

Which androgen receptor blocker’s main side effect is blood dyscrasias?

Answer 24

Flutamide

Question 25

Which androgen receptor blocker has a BBW for respiratory insufficiency (interstitial pneumonitis)?

Answer 25

Nilutamide

Question 26

What is a strange adverse effect of Nilutamide?

Answer 26

increased time to transition from light to dark

Question 27

MOA: Alkylating agent + estradiol structure (target EBP on prostate cancer to deliver alkalyating agent (microtubule inhibitor → disassembly, G2/M arrest, and DNA strand breaks). Inhibits testosterone by negative feedback on GnRH

Answer 27

Entramustine

Question 28

List the GnRH agonists that work by providing continual drug stimulation of the GnRH receptors in the pituitary--> the receptors down regulate secretion of FSH and LH is attenuated

Answer 28

Goserelin Histerelin Leuprolide Triptorelin

Question 29

List the reversible GnRH antagonist.

Answer 29

Degarelix (SC)

Question 30

Which works faster, GnRH agonists or angatonists?

Answer 30

GnRH antagonists

Question 31

MOA: Inhibitor of 17-alpha hydroxylase (CYP17) which prevents conversion of pregnenolone or progesterone to androgens (VERY SPECIFIC)

Answer 31

Abiraterone

Question 32

MOA: Culture patient APCs (leukapheresis) and culture with recombinant PAP-GM-CSF (APCs Take up antigen, process it, and express fragments on surface), renifuse product to stimulate CD8 T-cell immunity against prostatic acid phosphatase (PAP)

Answer 32

Sipuleucel-T

Question 33

What drug is commonly taken with abiraterone?

Answer 33

steroid

Question 34

TOXICITY: Prolonged treatment produces elevated levels of estradiol (gynecomastia, mastalgia, impotence, increased CV risk factors—edema, TE, MI, PE and stroke); GI Upset; elevated hepatic enzymes and hyperbilirubinemia

Answer 34

Entramustine

Question 35

TOXICITY: Decrease in bone mineral density (low estrogen), Increased CV risk (elevated serum lipids, weight gain and DN), Sexual dysfunction, loss of libido, gynecomastia; CNS problems (seizures/suicide with HIS only); TERATOGEN (Cat X)

Answer 35

Goserelin Histerelin Leuprolide Triptorelin

Question 36

TOXICITY: QT prolongation, hepatic enzyme changes; hot sweats, injection site RXN, weight gain, HTN, arthralgia, chills, fatigue, impotence

Answer 36

Degarelix

Question 37

TOXICITY: Tends to produce hypermineralocorticoid state→ HTN, hypoK and edema watch out for CV history (provides more substrates for that pathway); Teratogen; elevated hepatic enzymes

Answer 37

Abiraterone

Question 38

Why must you withdrawal abiraterone slowly?

Answer 38

adrenocortical insufficiency if withdrawn quickly

Question 39

TOXICITY: Mild infusion RXN; fever/chills/ dyspnea, GI effects (N/V); Paresthesias, cirtrate toxicity and fatigue

Answer 39

Sipuleucel-T

Question 40

What conventional chemo drugs are used in prostate cancer?

Answer 40

Docetaxel Carbazitaxel MItoxantrone

Question 41

What is the indication for carbazitaxel? Why?

Answer 41

Poor substrate for the multidrug resistance P-glycoprotein efflux pump (good for treating multidrug-resistant tumors)

Question 42

What is the indication for mitoxantrone?

Answer 42

Palliation of severe pain from advanced hormone refractory disease

Question 43

What do you take with mitoxantrone?

Answer 43

prednisone

Question 44

What conventional chemotherapy drug for prostate cancer can cross the BBB?

Answer 44

carbazitaxel

Question 45

What is the MOA of Mitoxantrone?

Answer 45

type II topoisomerase inhibitor; disrupts DNA synthesis/ repair in both healthy cells and cancer cells, by intercalation.

Question 46

What do you take with Carbazitaxel? Why?

Answer 46

Premedicate with corticosteroids +/- antihistamine blockers to pevent edema and injection reactions produced with these surfactant-containing drugs