epothilone-a and abiraterone

Castrate-resistant prostate cancer (CRPC) is a challenging aspect in the treatment of prostate cancer. Research has identified several pathways in the pathogenesis of CRPC. Several new agents targeting some of these pathways have shown promising data during clinical trials. In the area of androgen depletion, abiraterone acetate and MDV100 have been studied and have shown to decrease prostate-specific antigen (PSA) levels in phase I and II studies. Bevacizumab is a monoclonal antibody antiangiogenesis agent that targets vascular endothelial growth factor (VEGF) and has shown to decrease PSA levels in combination with other cytotoxic agents. Three agents, ixabepilone, patupilone, and sagopilone, in the class of epothilones (tubulin polymerizing antitumor agents), have shown moderate reductions in PSA levels and moderate adverse effects. The results of ongoing studies with these new treatment agents may offer viable alternatives to the traditional treatment of CRPC to decrease disease progression and improve overall survival.

Topics: Androstenes; Androstenols; Angiogenesis Inhibitors; Antibodies, Monoclonal, Humanized; Bevacizumab; Clinical Trials as Topic; Epothilones; Humans; Male; Prostatic Neoplasms; Steroid 17-alpha-Hydroxylase; Tubulin Modulators

Despite that greater knowledge of prostate cancer biology has led to the isolation of many new and promising targets, treatment of metastatic prostate cancer is still challenging. New agents targeting these molecules are currently under development in large randomized phase III trials, to improve overall survival and the quality of life of patients with metastatic castrate-resistant prostatic cancer (CRPC). Cytotoxic chemotherapy (docetaxel-based chemotherapy) demonstrated clinical benefit on overall survival, but could be improved. Drugs targeting directly or not the androgen receptor such as abiraterone or new specific peripheral anti-androgens (MDV3100) are very promising. Bone targeted therapies (endothelin1 receptor A inhibitor, RANK ligant, metabolic irradiation) are also very promising and are in development in large phase III trials. Antiangiogenic therapies could also be effective in CRPC. Autologous vaccin against prostatic acid phosphatase seems to prolong overall survival and other vaccin and immunotherapy strategies are in development (anti-CTLA4 antibody). A recent analogue of thalidomide, probably more efficient, lenalidomide is also in development.

Topics: Androgen Antagonists; Androstenes; Androstenols; Angiogenesis Inhibitors; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents, Hormonal; Bone Neoplasms; Castration; Denosumab; Epothilones; ErbB Receptors; Furans; Humans; Immunotherapy; Ketones; Male; Orchiectomy; Prostatic Neoplasms; Pyrrolidines; RANK Ligand