Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Februray, 2013 The Return of My Cancer -Emerging Effective Therapies Jianqing Lin, MD Why/How my cancer is back after surgery and/or radiation? • Undetected micro-metastatic disease (spreading) before local treatment • … What are the treatment options now? • Informed decision making to improve patient care and survival • Individualized care (personalized medicine): goal • Disease state dependent 70-80% 20-30% Death from disease Death from co-morbidities Prostate cancer clinical-states model Scher et al: J Clin Oncol 26:1148-1159 Early Presentation: • Cancer may come back in the prostate or in other parts of the body • May need re-biopsy to confirm (local or distant spots) • Urinary symptoms (weak flow of urine or frequent urination etc) • Bone pain related to disease • Most patients: rising PSA without symptoms What is Prostate-Specific Antigen (PSA)? • A glycoprotein discovered in 1970s, • An enzyme produced by prostate gland, secreted into the male ejaculate, regulated by male hormone (androgen receptor), • Abnormal PSA: – Benign conditions: BPH, prostatitis, prostate infarct or manipulation etc. not cancer specific – Cancer specific if prostate is removed already or radiated – Monitoring changes of PSA is recommended after local treatments Natural History of a Rising PSA after surgery (“old data”) Time from RP to a rising PSA 2 years Time from BCR to clinical metastases 8 years Time from clinical metastases until death 5 years Life expectancy after failed surgery 15 years Pound CR, et al. JAMA. 1999; 281:1591-1597. Diagnostic studies and re-staging • CAT scan and bone scan to rule out distant metastasis, – Positive – Negative • MRI pelvis to determine local recurrence. • If scans are negative, your cancer maybe still local, may still be cured: – Additional radiation; or – Salvage surgery Treatment options for recurrent prostate cancer • Additional radiation therapy (called salvage radiation): after surgery or seeds radiation. • Prostatectomy (initially treated with radiation, rarely done). • Hormone therapy What is hormonal therapy? • Treatment that adds, blocks, or removes hormones. • For prostate cancer, it is to slow or stop the growth of cancers • Drugs may be given to block the body’s natural hormones. Sometimes surgery is needed to remove the gland that makes a certain hormone. • Also called endocrine therapy, and hormone treatment. • Approved for metastatic prostate cancer treatment Hormonal Therapy for Prostate Cancer (traditional) Hormone therapy Advantages disadvantages note Orchiectomy Cost-effective Permanent, disfiguring LHRH agonist reversible expensive leuprolide, goserelin LHRH antogonist reversible expensive Degarelix (Firmagon) Anti-androgen therapy Noncastrating, improved energy, libido, potency Expensive, gynecomastia flutamide, bicalutamide, nilutamide, 5 reductase inhibitors; ketoconazole CAB reversible Expensive, increased side effects No evidence of superior to LHRH alone CAB: Combined androgen blockade, Estrogen therapy (DES, PC-SPES): Not used now Negative Aspects of Androgen Deprivation • Hot flashes (Megesterol acetate, anti-depressants, phytoestrogens) • Loss libido / erectile dysfunction (sildenafil, vardenafil, tadalafil) • Bone mineral loss/ accelerated osteopenia (zolendronic acid, risedronate, alendronate, calcium, vitamin D) • Weight gain • Changes in lipid/ glycemic metabolic profiles (?insulin sensitizing agents, lipid lowering, high blood pressure meds) • Anemia (erythropoeitin) • Neuro-cognitive changes Long Term side Effect of Androgen Deprivation Therapy Hyperglycemia Insulin Resistance Metabolic Complications of ADT Metabolic Syndrome Dyslipidemia Treatment options for recurrent prostate cancer • Additional radiation therapy (called salvage radiation): after surgery or seeds radiation. • Prostatectomy (initially treated with radiation, rarely done). • Hormone therapy • Biologic therapy (ie, Sipuleucel-T) (already treated with hormone therapy), Provenge Treatment Process PROVENGE (Sipuleucel-T)—cellular immunotherapy • Approved by FDA on 4/29/10 • Consisting of autologous peripheral blood mononuclear cells, including antigen presenting cells (APCs), that have been activated during a defined culture period with a recombinant human protein, PAP-GM-CSF, an immune cell activator. • Process: 1) standard leukapheresis to obtain PBMC 3 days prior to the infusion date; 2) ex vivo culture with PAP-GM-CSF, the recombinant antigen binding to and being processed by APCs; 3) Infusion back to patient • Extend life for 4.1 months (median) Androgen Receptor: remains a key target for treatment • New finding: “hormone-refractory” cancer still needs androgen to grow still androgen sensitive -> term changes castrate resistant; • Newly approved drugs: – Abiraterone (Zytiga): • Oral • Inhibits testosterone synthesis/production in testis, adrenal glands and prostate, and cancer cells – Enzalutamide (Xtandi): • Oral • pure antiandrogen/novel androgen receptor blockade • More are coming Treatment options for recurrent prostate cancer • Additional radiation therapy (called salvage radiation): after surgery or seeds radiation. • Prostatectomy (initially treated with radiation, rarely done). • Hormone therapy • Biologic therapy (ie, Sipuleucel-T) (already treated with hormone therapy), • Chemotherapy, Chemotherapy • • • • More toxic but generally tolerable Intravenously given Need to be followed more closely Two drugs proved to prolong life: – Docetaxel (Texotere) first line – Cabazitaxel (Jevtana): second line Treatment options for recurrent prostate cancer • Additional radiation therapy (called salvage radiation): after surgery or seeds radiation. • Prostatectomy (initially treated with radiation, rarely done). • Hormone therapy • Biologic therapy (ie, Sipuleucel-T) (already treated with hormone therapy), • Chemotherapy, • Bone targeted treatment Bone Targeted Therapies • Vitamin D and Calcium daily • Denosumab (Xgeva) – To prevent bone loss, bone damage from cancer such as fractures – Every 4 – 6 weeks – Mild side effects but needs to be monitored regularly • Bisphoshonates: – Zometa – Similar to Xgeva – Need to monitor kidney function • Radiopharmaceuticals (liquid radiation): – Alpharadin or – samarium RANKL: receptor activator of nuclear factor κ- B ligand Treatment options for recurrent prostate cancer • Additional radiation therapy (called salvage radiation): after surgery or seeds radiation. • Prostatectomy (initially treated with radiation, rarely done). • Hormone therapy • Biologic therapy (ie, Sipuleucel-T) (already treated with hormone therapy), • Chemotherapy, • Bone targeted treatment • Palliative therapy ( to lessen bone pain): Pain control, external radiation therapy, internal radiation therapy with radioisotopes), Treatment options for recurrent prostate cancer • Additional radiation therapy (called salvage radiation): after surgery or seeds radiation. • Prostatectomy (initially treated with radiation, rarely done). • Hormone therapy • Biologic therapy (ie, Sipuleucel-T) (already treated with hormone therapy), • Chemotherapy, • Palliative therapy ( to lessen bone pain): Pain control, external radiation therapy, internal radiation therapy with radioisotopes), • Clinical trials: – Many – Most : new anticancer drugs (+/- radiation). Emerging therapies for recurrent prostate cancer • Additional radiation therapy (called salvage radiation): after surgery or seeds radiation. • Prostatectomy (initially treated with radiation, rarely done). • Hormone therapy: Firmagon, Zytiga, Xtandi etc • Biologic therapy (ie, Sipuleucel-T) (already treated with hormone therapy), • Chemotherapy, • Palliative therapy ( to lessen bone pain): Pain control, external radiation therapy, internal radiation therapy with radioisotopes), • Clinical trials: – Many – Most : new anticancer drugs (+/- radiation). Summary • A disease of long nature history • Relax, don’t be panic • Survivorship: a multimodality approach, primary care MD’s involvement is key • Bone is the most common metastatic site -> Bone-targeted therapy reduce risk of fracture • Androgen deprivation is main stay of treatment for advance PCa but has side effects • Androgen-AR axis remain the main target for the treatment of PCa novel drugs, less toxic • Chemotherapy, active immune-therapy improve survival • Many drugs are on the way clinical trials are highly encouraged Questions and Discussion