Drugs for Prostate Cancer Flashcards
What is unique pharmacologically about prostate Cancer?
Prostate cancer is the most hormone sensitive of all cancers. Also one must take into account 2 sources of androgens (Testis and Adrenals).
What is the first line treatment for prostate cancer?
Medical or surgical castration plus pure anti androgen drug is the first line treatment. Radiation may be an alternative treatment.
What are some drug targets for prostate cancer therapy?
Pituitary release of ACTH/LH
CYP17A1 (17-hyroxylase)
Androgen receptors
What are the GnRH agonists that are used to treat prostate cancer?
Goserelin
Histarelin
Leuprolide
Triptorelin
What is the MOA for the GnRH agonists in treating prostate cancer?
Continuous GnRH downregulates GnRH receptors thus decreasing the production of LH/FSH. The result is lower levels of sex hormones. However, there is an initial increase in GnRH receptor activation which can cause a disease flare.
What are some adverse effects which are common to the GnRH class?
Decreased bone density increased triglycerides Weight gain Sexual dysfunction, gynecomastia, Pregnancy Category X
Which GnRH agonists can be given SC?
Goserelin
Histarelin
Leuprolide
Which GnRh agonists can be given IM?
Leuprolide
Triptorelin
What adverse effects are unique to Histarelin?
Seizure
Suicide
WHat adverse effects are unique to Leuprolide?
MI
CHF
What is the MOA of Degarelix?
Degarelix is a GnRH antagonist. Has the same long term effect as the GnRH agonists, except there is no initial disease flare and castration occurs in 3 days.
How is Degarelix administered?
SC
What adverse effects are associated with Degarelix?
More important:
Elevated LFTs, Hepatotoxicity
QT prolongation, HTN
Less Important: Hot flashes Injection site rxn impotence Arthralgia
Which drugs are the androgen receptor blockers?
Bicalutamide
Enzalutamide
Flutamide
Nilutamide
What is the MOA of the androgen receptor blockers?
Obviously they block the effects of stimulatory effects of Testosterone and DHT on the tumor. (stupid question)
What are some common adverse effects of the Androgen receptor blockers?
GI Toxicity
Hot flashes
Arthralgia/Myalgia
Teratogenic (except Nilutamide)
What is unique about Bicalutamide?
Bicalutamide is an agonist and an antagonist with more effect in the prostate than centrally. Also known for CYP interactions
What is unique about Enzalutamide?
Enzalutamide has effects both in the prostate and centrally. Unique adverse effects include: Seizures URTI Male teratogenicity
What is unique about Flutamide?
Flutamide has effect in the prostate only. Unique adverse effects include Hepatotoxicity (BBW), and blood dyscrasias.
What is Unique about Nilutamide?
Nilutamide has effect in both the prostate and centrally. Unique adverse effects include: Interstitial pneumonitis CHF/HTN Blood dyscrasias photosensitivity.
What is Estramustine?
Estramustine is an estrogen with an alkylator attached to it.
What is the MOA of Estramustine?
Binds estrogen binding protein on prostate cancer and delivers the alkylator which inhibits microtubules and causes DNA strand breaks.
What adverse effects are associated with Estramustine?
PE/DVT, MI, Stroke GI tox gynecomastia, mastalgia Impotence, edema increase LFTs.
What is the MOA of Sipuleucel?
Sipuleucel involves taking the patients APCs, modifying them, and then putting them back in. They new APCs stimulate T cell immunity to prostatic acid phosphatase.
What adverse effects are associated with Sipuleucel?
Parathesia,
Citrate toxicity
GI disturbance
Dyspnea
What is the MOA of Abiraterone?
Abiraterone inhibits 17-hydroxylase. This prevents the production of DHEA and Androstenedione.
What adverse effects are associated with Abiraterone?
Increased mineralcorticoids (Suppress with ACTH) Increased LFTs CAT X (use condoms b/c semen may spread drug)
Why aren’t 5-alpha-reductase inhibitors used to treat prostate cancer?
b/c they increase the risk of cancer (possibly?)
What is the difference in the various estrogen receptors in the prostate?
Estrogen receptor Alpha promotes inflammation and malignant proliferation
Estrogen receptor beta is anti-inflammatory and reduces proliferation
What is the conventional chemotherapeutic therapy for metastatic prostate cancer?
Taxanes
Mitoxantrone (used for palliation in severe Dz)
