Current and emerging treatments in the management of castration-resistant prostate cancer

Abstract

Historically, patients diagnosed with castration-resistant prostate cancer (CRPC) have had poor survival rates. In recent years there have been significant advances in the treatment of CRPC. In addition to cytotoxic chemotherapy, treating physicians and their patients now have the option of several new agents that target not only androgen- and cytotoxic-mediated pathways, but also the patient's own immune system. In this review, we discuss the existing US FDA-approved therapies, a wide range of experimental treatments that are currently in development, and also palliative options for patients with symptoms secondary to metastatic disease. We also discuss the progression-free survival, overall survival, PSA levels and other end points used in clinical trials in order to evaluate and compare novel therapeutic options for CRPC. Currently, docetaxel and sipuleucel-T are the first line treatment options for patients with CRPC; approved second-line treatments for first line treatment failure are limited to cabazitaxel and abiraterone acetate. Recently, a few experimental agents, MDV3100 and radium-223, have demonstrated efficacy in improving overall survival in patients who had previously failed chemotherapy. These agents, and possibly others introduced in this review, are positioned to change the treatment landscape for CRPC.

EZH2, an epigenetic driver of prostate cancer

“…Nevertheless, a majority of the tumors can evolve from a hormone-sensitive to a hormone-refractory state, termed castration-resistant prostate cancer (CRPC), which often results in lethality in 1–2 years (Berry et al, 2002; Higano et al, 2009; Lassi and Dawson, 2009; Kantoff et al, 2010a, 2010b). Even with current therapeutic options that are available, such as docetaxel plus prednisone, cabazitaxel, abiraterone acetate, sipuleucel-T as well as the most recently FDA-approved enzalutamide (formerly known as MDV3100) (Shapiro and Tareen, 2012), CRPC still presents a great clinical challenge.…”

Bone-targeted Novel Cytotoxic Polybisphosphonate Conjugate in Castration-resistant Prostate Cancer: A Multicenter Phase 1 Study

“…Although the last decade has resulted in a handful of new approved drugs, i.e. drugs that improve the overall survival time for CRPC patients (10)(11)(12)(13)(14), there is an unmet need for new drugs with a positive impact on survival and quality of life. Quality of life is intimately related with side- effects of the drugs that are used for treating the CRPC patient.…”

Clinical appraisal of abiraterone in the treatment of metastatic prostatic cancer: patient considerations, novel opportunities, and future directions

“…Within a course of less than 2.5 years, four new therapeutic modalities became available to patients with castration-resistant prostate cancer in the post-docetaxel setting: the taxane cabazitaxel (Jevtana), the immunotherapeutic sipuleucel-T (Provenge), the CYP17 inhibitor abiraterone acetate (Zytiga), and the second-generation AR antagonist enzalutamide (Xtandi) 9,10. At this moment, no data are available to guide oncologists and patients in their choice between these agents.…”

“…Furthermore, no biomarkers are available to help predict sensitivity to any of these agents, thus further complicating clinical decision-making. It is reasonable to anticipate that the nonchemotherapy approaches will be favored (by both patients and physicians) to be used prior to cabazitaxel (mainly due to the significant toxicity of the latter) 9,10. As none of these approaches is curative, we anticipate that all patients will be eventually treated sequentially with all these agents.…”