Tx of Prostate Cancer Flashcards
Is prostate cancer typically hormonally responsive?
Yes! Just like breast, endometrial, and adrenocortical carcinomas. Thus, drug therapy is tailored around blocking hormone sensitivity
What is the first line treatment for prostate cancer?
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)
Like other hormonally responsive tumors, a prostatic tumor can evolve into an androgen-insensitive growth pattern. How?
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
How does GnRH agonism down-regulate hormonally responsive tumor growth?
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
What are some GnRH analogs?
Goserelin, Histrelin, Leuprolife, and Triptorelin (continuous administration results in chemical castration in about 2-4 weeks).
Given SC mostly
What are the common AEs of GnRH analogs?
symptoms that would be expected of a castration including hot flashes, decreased libido, ED, osteoporosis (no estrogen), and gynecomastia
Category X preg
What is a GnRH receptor antagonist? Onset? AEs?
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
What is Estramustine (Emcyt)?
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
AEs of Estramustine?
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
What are some other effects of having elevated estrogen levels with prolonged estramustine therapy?
edema, thromboembolism
MI, stroke and PE
What are some androgen receptor blockers?
Flutamide, Nilutamide, Bicaulatamide, and Enzalutamide
NOTE: Spironolactine also inhibits androgen receptors and can be used to treat hirsutism in women
Describe the androgren receptor blockers
These are PO non-steroidal blockers which diminish androgen-driven tumor proliferation
What are the AEs of the ARBs?
Common AEs of lack of estrogen including hot flashes, decreased libidio, ED, etc.
What are the other uses of Flutamide?
tx of hirsutism or polycystic ovary syndrome