Neuroendocrine Dedifferentiation in Progressive Prostate Cancer: New Therapeutic Approaches

Introduction

The prognosis for metastatic castrate-resistant prostate cancer (mCRPC) is limited, with a median survival without treatment of about 12 months. However, recent studies have evaluated the efficacy of various cytotoxic compounds in improving these statistics. Taxanes, in particular docetaxel, have demonstrated efficacy and are the therapeutic standard. Docetaxel was approved in combination with prednisone on the basis of results from the phase III TAX 327 study, which showed superior overall survival for the combination compared with mitoxantrone and prednisone 1. The combination of docetaxel and estramustine has also demonstrated improved progression-free and overall survival compared with mitoxantrone and prednisone in patients with mCRPC 2, 3; however, the value of this addition has not yet been established fully. Epothilones, a new cytotoxic class, have also demonstrated benefit in terms of objective response and progression time, in particular with the combination of ixabepilone and estramustine in a phase II study 4; but new compounds that impact overall survival are still needed for the treatment of advanced prostate cancer.

Abstract

Keywords

castrate-resistant prostate cancer, neuroendocrine, chromogranin A, somatostatin, cisplatin, docetaxel, etoposide, carboplatin