Tx of Prostate Cancer Flashcards

1
Q
A
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2
Q

Is prostate cancer typically hormonally responsive?

A

Yes! Just like breast, endometrial, and adrenocortical carcinomas. Thus, drug therapy is tailored around blocking hormone sensitivity

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3
Q

What is the first line treatment for prostate cancer?

A

combined androgen blockade- medical or surgical castration plus a pure anti-androgen. Other non-drug approaches include watchful waiting and external beam irradiation of the prostate, as well as implanted I125 titanium coated seeds used to treat early stage disease (a technique called brachytherapy)

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4
Q

Like other hormonally responsive tumors, a prostatic tumor can evolve into an androgen-insensitive growth pattern. How?

A

Usually there are changes in AR amplication, by point mutation and changed in co-regulatory proteins. Such effects result in a ‘super-AR’ that can respond to lower conc. of androgens or the ability to function in a ligand-independent manner

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5
Q

How does GnRH agonism down-regulate hormonally responsive tumor growth?

A

Normally, GnRH release is pulsatile so the continuous administration of GnRH can down-regulate pituitary receptors and ultimately decrease FSH and LH production. Note that there is an initial transient disease flare that is best managed by co-administration of an androgen receptor blocking drug

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6
Q

What are some GnRH analogs?

A

Goserelin, Histrelin, Leuprolife, and Triptorelin (continuous administration results in chemical castration in about 2-4 weeks).

Given SC mostly

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7
Q

What are the common AEs of GnRH analogs?

A

symptoms that would be expected of a castration including hot flashes, decreased libido, ED, osteoporosis (no estrogen), and gynecomastia

Category X preg

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8
Q

What is a GnRH receptor antagonist? Onset? AEs?

A

Degarelix (Firmagon). This drug is given SC and because it inhibits GnRH receptors directly, produces a much quicker onset than GnRH analogs and avoids the initial hormone flare associated with analogs

AEs are similar to GnRH analogs

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9
Q

What is Estramustine (Emcyt)?

A

A PO drug that is a conjugated drug with an alkylating moiety attached to its estradiol structure. By targeting the estramustine binding protein on prostate tumors, it delivers the alkylator which functions as a microtubule inhibitor

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10
Q

AEs of Estramustine?

A

GI disturbances

gynecomastia, mastalgia, and impotence due to elevated levels of estradiol (similar to estrogen therapy)

  • depressed testosterone levels via nega. HP feedback
  • elevated LFTs and hyperbilirubinemia
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11
Q

What are some other effects of having elevated estrogen levels with prolonged estramustine therapy?

A

edema, thromboembolism

MI, stroke and PE

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12
Q

What are some androgen receptor blockers?

A

Flutamide, Nilutamide, Bicaulatamide, and Enzalutamide

NOTE: Spironolactine also inhibits androgen receptors and can be used to treat hirsutism in women

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13
Q

Describe the androgren receptor blockers

A

These are PO non-steroidal blockers which diminish androgen-driven tumor proliferation

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14
Q

What are the AEs of the ARBs?

A

Common AEs of lack of estrogen including hot flashes, decreased libidio, ED, etc.

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15
Q

What are the other uses of Flutamide?

A

tx of hirsutism or polycystic ovary syndrome

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16
Q

What is Sipuleucel-T?

A

This drug is essentially immunotherapy customized to individual pts. by taking APCs and processing them to seek out prostatic tumor cells by stimulating a T-cell response against prostatic acid phosphatase

17
Q

What are the AEs of Sipuleucel-T?

A

Mild infusion rxns; fever/chillds, and dyspnea

paresthesias, citrate toxicity and fatigue

18
Q

What does the enzyme 17a- hydroxylase do?

A

it mediates conversion of pregnenolone to progesterone and subsequently to androgens. Thus androgens levels are reduced and prostatic tumors lose their proliferative signal.

19
Q

What is the difference between the effects of ketoconazole and 17a-hydroxylase inhibitors on adrenal hormone production?

A

Keto produces a hypo cortisol AND aldosterone state, while 17a inhibitors tend to produce a hyper-aldosterone state

20
Q

What is Abiraterone?

A

A CYP17 inhibitor (remember these produce a hyperaldosterone state- treat with a corticosteroid (prednisone) to reduce ACTH stimulation)

21
Q

What are the AEs of Abiraterone?

A

elevated LFTs

Cat X drug- thus women should not handle the drug and condoms should be used for sex during pregnancy b/c of the ability of the drug to pass via the semen is unknown

22
Q

How could prostate tumors be resistant to hormone targeting?

A

AR overexpression or mutations that promote ligand independence

increased androgen production and reduction in tumor suppressors

23
Q

How would the use of estrogens such as estradiol, DES, and ethinylestradiol be used to reduce testosterone levels?

A

They would feedback on the HP axis. These drugs are very protective to bone health BUT CV AEs have led to a reduction in use of these drugs in prostate cancer tx (but there has been some renewed interest in transdermal estrogen which has less CV effects than oral estrogen)

24
Q

Note that the use of 5a-reductase inhibitors is still controversial in prostate cancer treatment/prevention

A
25
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A
26
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A
27
Q

What are the conventional chemo drugs used in prostatic cancer tx?

A

Docetaxel and carbazitaxel for metastatic prostatic cnacer (both use premedication with corticosteroids and anti-H1/H2 histamine blockers to preemptt edema and injection rxns produced with these surfactant-containing drug preps)

Mitoxantrone (+ prednisone) for palliation of severe pain for advanced hormone-refractory disease

28
Q

T or F. Unlike other taxanes, Cabazitaxe is a poor substrate for the multidrug resistance P-glycoprotein efflux pump and may be useful for trating multi-drug resistant tumors

A

T. In addition, cabazitaxel penetrates the BBB, where Pgp efflxu pumps may serve as barriers

29
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30
Q
A

All

31
Q
A

B

32
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A