Castration Resistant, Taxane Naïve Metastatic Prostate Cancer: Current Clinical Approaches and Future Directions

Abstract

With the wide use of prostate specific antigen to detect response and disease progression resistance to androgen deprivation is being detected at an increasingly earlier stage. We focused on the current management and novel investigational strategies for the chemonaïve patient population with castration resistant metastatic disease. We reviewed standard and investigational hormonal, chemotherapeutic, biological and immune based strategies for patients with castration resistant metastatic prostate cancer who have not yet received taxane based chemotherapy. Our understanding of the natural history of this group of patients is evolving. A variety of standard and experimental treatment options are available for this group of patients. Manipulating the androgen receptor signaling axis, targeting antiapoptotic pathways, using antiangiogenic strategies, harnessing the immune system and optimizing docetaxel based regimens and novel cytotoxic agents are under investigation. Multiple agents currently under development offer a promise of palliation and prolongation of survival above and beyond that of docetaxel. In the absence of guidance from randomized trials with regard to chemotherapy timing, and considering the modest effects of docetaxel on survival, decisions regarding choice of therapy (standard chemotherapy or experimental therapies) must be based on careful consideration of the functional status of each individual, presence of symptoms, comorbidities and overall therapeutic objectives.