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Oncology II
Prostate Cancer and Hormonal Therapy
Term | Definition |
---|---|
What is the prostate screening recommendations? | - for prostate cancer after the age of 50y/r - the frequency depends on the type of screening |
what is the survival rate of patients diagnosed with prostate cancer? | - pt diagnosed with non- metastatic cancer--> survival rate is high - pt diagnosed with metastatic cancer --> Mortality rate is high |
What is the recommended treatment for pt diagnosed with non- metastatic prostate cancer? | - surgery - radiation - +/- ADT |
What is the recommended treatment for pt diagnosed with metastatic prostate cancer? | - depends on castration resistance 1- if NO: ADT + GnRH ( blocker/agonist) 2- If yes: cytotoxic chemo or other hormonal agents |
What is the main MOA of hormonal therapies in patient with prostate cancer? | - reduce the level of testosterone +/- blocking the receptors |
what are some common side effects of using hormonal therapy - ADT drugs? | hypogonadism like sxs: 1- hot flashes 2- loss libido 3- gynecomastia 4- hair thin 5- peripheral edema |
what are some complications a patient receiving ADT drugs may experience? | 1- hyper- lipid 2- DM 3- wt gain 4- osteoporosis 5- metabolic complications 6- QT prolongation ****** |
What is the MOA of GnRH agonists? | - LH hormone releasing hormone agonists ( LHRH ) - suppression of testosterone level via negative feedback MOA |
what is the MOA of GnRH induced tumor flare? | - LHRH --> Causes initial surge in testosterone level ---> tumor flare in pt with metastatic prostate cancer |
what is the recommended prevention of GnRH induced tumor flare? | - anti androgens for several weeks in conjunction with the initiation of GnRH agonist |
List the common GnRH agonist drugs? | - Leuprolide - Goserelin - Histrelin - Triptorelin - Degarelix** |
Which GnRH agonists are used to treat women with breast cancer? | - leuprolide - goserelin ( leu + gose) |
which GnRH agonist doesn't induce tumor flare? | Degarelix ( relax no flare) |
What are some preventable approaches if GnRH agonist is to be used? | - osteoporosis ( vit D and Ca + screening + exercise) - tumor flare ( anti androgen) |
when is the use of leuprolide C/I? | - vaginal bleeding |
when are the use of GnRH agonist C/I? | - pregnancy ( All including degarelix) - breastfeeding |
what are some common side effects of GnRH agonist? ( low testosterone) | - hot flashes - impotence - gynecomastia - peripheral edema - bone pain - QT prolongation - hyper lipid - hyperglycemia - |
Which GnRH agonist doesn't cause tumor flare upon initation? | Degarelix |
what is the main side effect seen with degarelix use?? | hypersensitivity rxn-- SC injection/month |
what is the common suffix of GnRH agonist? | - Relin except leuprolide and degarelix |
what us unique about GnRH route of administration? | - SC or IM injection ever month for up to 1 yr - SC ONLY for Degarelix |
what is the MOA of anti androgen in patient with prostate cancer ? | - competitive inhibition of of testosterone binding to prostate cells |
Why anti androgen is not used as mono-therapy? | - NEVER USE AS MONO-THERAPY ( ineffective) 2/2 up regulation of testosterone receptor - USE WITH GnRH agonist |
1st generation anti androgen drugs? | - bicalutamide - flutamide - nilutamide |
which anti androgen drug causes onest of diarrhea? | flutamide |
which anti androgen drug cause night blindness ? | - niltuamide |
which anti androgen drug cause disulfiram reaction? | - niltuamide |
which anti androgen drug the patient should avoid drinking alchohol while taking it? | - niltuamide |
which anti androgen drug causes hepatotoxicity? | - flutamide |
which anti androgen drug causes interstitial pneumonitis? | - niltuamide |
which 1st generation anti androgen is used most often? | bicalutamide |
Which anti androgen is C/I if pt is pregnant? | bicalutamide |
Which anti androgen is C/I in severe hepatic impairment? | nilutamide and flutamide |
what are some common side effects of using anti androgen drugs? | - low testosterone level sxs: 1- hot flashes 2- gynecomastia 3- edema 4- asthenia 5- hepatotoxicity 6- Risk of CV 7- GI: n/v/d |
what makes the 2nd generation anti androgen different from the 1st generation? | - 1st generation: can't use MONO therapy ( up-regulation of androgen receptor + use with GnRH agonist) vs. - 2nd generation: CAN USE MONO therapy ( no up-regulation of androgen receptor) |
what are some common 2nd generation anti androgen? | ONE DRUG: Enzalutamide |
when is the use of enzalutamide C/I? | pregnancy |
which anti androgen drug induces/ causes seizure? ( Warning) | Enzalutamide |
what are some common side effects enzalutamide (2nd generation? | - HTN/ edema - hot flashes/ fatigue |
what is the MOA of Androgen biosynthesis inhibitor ( Abiraterone)? | - inhibits CYP-17 enzyme --> inhibits biosynthesis of steroid in testes and adrenal gland ---> less testosterone production |
why steroid should be given in conjunction with Abiraterone in patient with prostate cancer? | - Prednisone + abiraterone = negative feedback on aldosterone production - Prevention of HYPER aldosteronism |
explain why prednisone is given with abiraterone ( androgen biosynthesis inhibitor)? | 1- androgen biosynthesis inhibitor --> inhibits steroid production 2- low steroid --> more aldosterone production --> hyper aldosteronism 3- using prednisone prevents hyper aldosteronism |
When is the use of Abiraterone is C/I? | pregnancy |
what are some common side effects of Abiraterone? | - mineralocorticoid excess ( hyper aldosteronism): 1- HTN 2- fluid retention 3- HYPO K 4- HYPO PO4 |
what are some common side effect of abiraterone? | - Hepatotoxicity - HYPER glycemic - increases TG |
What is the dosing of abiraterone in patient with prostate cancer? | - 1000mg/day ( 4 tablets of 250mg) - GIVEN WITH prednisone 5mg BID to prevent Hyperaldosteronism |
when is abiraterone is dose adjusted? | concurrent use of CYP 3A4 inducers |
what is the appropriate timing of anti androgen drugs to be started in conjunction with GnRH as prevention ( tumor flare) ? | - 1 week prior to chemo |