LUNCH AND LEARN April 17, 2018 David R. Wilkinson M.D. Gulfshore Urology
Medical Therapy for Prostate Cancer Androgen (testosterone) is required for the growth of both normal prostate and prostate cancers Early in its development, the great majority of prostate cancer needs high levels of testosterone, this is ANDROGEN SENSITIVE, prostate cancer. Given enough time, most prostate cancers will figure out how to grow without testosterone, this is ANDROGEN INSENSITIVE or CASTRATE RESITANT. Cancer that is castrate resistant is able to grow with low or undetectable levels of testosterone Testosterone < 80ng/dl is considered castrate or equivalent to the removal of the testicles
Two types of castrate resistant cancer Metastatic; Radiographic or biopsy evidence of cancer outside the prostate Non-metastatic; No radiographic or tissue evidence of cancer outside the prostate
Surgical, hormonal Treatment of androgen sensitive prostate cancer Castration: The surgical removal of the testicles Whole testicle removal called orchiectomy Removal of the portion of the testicles that produces testosterone is called subcapsular orchiectomy
Medical treatment of androgen sensitive prostate cancer (or medical castration) Casodex (bicalutamide) Androgen receptor blocker, non steroidal Can block the androgen receptors in testicles and adrenal glands Cost effective, about 18 dollars for 30 tablets Side effects: fatigue, weight gain, decreased libido, erectile dysfunction, breast tenderness and breast tissue growth in males.
LHRH or GnRH Agonists Luteinizing hormone releasing hormone When testosterone levels in the body are low, LHRH stimulates pituitary gland to produce luteinizing hormone, which in turn stimulates the testicles to produce testosterone LHRH agonists mimic the action of luteinizing hormone and cause and initial surge of testosterone. The continued high levels of LHRH and testosterone then tell the pituitary gland to stop producing luteinizing hormone and therefore testosterone production stops
3 FDA approved LHRH agonists Lupron 1 month, 3 month and 6 month injections. First FDA approved 1989 Eligard 1month, 4 month and 6 month injections Firmagon Initial dose 240mg one month injection Maintenance dose 88mg one month injection Between 1300 and 1500 dollars per injection
Side effects of LHRH Agonists Fatigue, weight gain, decrease libido, erectile dysfunction, breast tenderness and male breast growth Bone density loss Type 2 diabetes, or insulin resistance (pre-diabetes) Hyperlipidemia Cardiac disease
Metastatic, Castrate Resistant Prostate Cancer 2004 Docetaxal 2010 Provenge 2010 Jevtana 2011 Zytiga 2012 Xtandi 2013 Xofigo
Non-Metastatic, Castrate Resistant Prostate Cancer 2018 Erleada
Docetaxal Given in conjunction with prednisone (steroidal inhibition of testosterone production) Chemotherapy given by Oncologist Inhibits micro tubular depolymerization Decreases effects if bcl-2 and bcl-8l genes (genes important in cancer growth and survival) Improves survival by 18.9 months (median) Significant improvement in comparison with initial chemotherapy mitoxatrone and prednisone (which did not increase survival, but increased quality of life) 23,000 per month
Docetaxal Side Effects Nausea, vomiting, diarrhea, constipation Low white blood cell counts Elevated triglycerides Fatigue Anemia Renal insufficiency
Provenge Tumor vaccine Autologous cellular immunotherapy used to stimulate patients own immune system Prostate cancer is immuno-evasive (not recognized by the immune system Immune system is taken out of patients blood stream, exposed to prostate cancer in the lab, and then returned into the patients body Patients Antigen Presenting cells are then matured or recognize prostate cancer and identify prostate cancer cells for T cells which fight the cancer Extends life expectancy with advanced prostate cancer by about 4 months 93,000 dollars for 4 month course
Jevtana Chemotherapy Used in conjunction with prednisone Used when docetaxal fails (cancer progresses on docetaxal) Binds to microtubules of cancer cells to make them rigid, therefore slows or prevents rapidly dividing cells from dividing. Some cancer cells respond, some do not Reduced risk of death by 30% and prolonged survival by 15.1 months average 10,000 dollars per month, given every 3 weeks
Jevtana Side Effects Low whit blood cell counts (suppressed immune system) Low red blood cell counts (anemia) Low platelet count (bleeding issues) Shortness of breath Loss of taste Hair loss Joint pain or swelling
Zytiga (arbiraterone acetate) Pill, 2 to 4 per day for total dose of 1000mg Prednisone 5mg twice daily with Blocks production of testosterone in testicles, adrenal glands and in prostate cancer cells Inhibits CYP17, enzyme required for testosterone production in all of the above Increases survival with advanced prostate cancer average of 34.7 months Delayed the start of chemotherapy and average of 24.7 months 5000 dollars per month
Zytiga side effects Increased triglycerides Insulin resistance and increased blood sugar Liver toxicity Elevated blood pressure Increased blood sodium Joint pain or swelling Muscle aches/myalgias Constipation/diarrhea
Xtandi (enzalutamide) NO PREDNISONE Androgen receptor inhibitor 4 total pills per day 23% reduction in risk of death Median overall survival 35.3 months Delayed start of chemotherapy aver of 28 months
Xtandi Side Effects Seizures Posterior Reversible Encephalopathy Syndrome (PRES): Seizure, headache, lethargy, blindness or visual disturbances, High Blood pressure. Fractures with fall Fatigue, back pain, joint pain or swelling, decreased appetite, constipation, hot flashes, upper respiratory infection
Xofigo (Radium 223) ONLY for treatment of castrate resistant prostate cancer to BONES 6 injections, every 4 weeks Alpha particle emitter Combines with bone mineral hydroxyapatite in areas of cancer metastasis 69,000 for 6 total injections Significantly decreases bone pain and reduces risks of fractures
Xofigo Side Effects Nausea, vomiting, diarrhea Swelling of arms and legs Low red blood cell and white blood cell counts
Non-Metastatic, Castrate Resistant Prostate cancer Erleada, 2018
Erleada (apalutamide) Pill form No prednisone Androgen receptor inhibitor, binds directly to the ligand binding domain (think of dock behind your home) of the androgen receptor (your home) and therefore no new DNA for cancer can be made and therefore no new cancer cells. Decreased the risk of distant metastasis and death by 72% Improved median survival by 24 months 10,900 dollars per month