Future Directions in Metastatic Castration Resistant Prostate Cancer (mCRPC): Clinical Rationale and Use of New-Generation Hormonal Therapies

Paolo Grassi, Elena Verzoni, Rosanna Montone, Isabella Testa, Enrico Garanzini, Pamela Biondani, Sara Pusceddu, Filippo de Braud, Giuseppe Procopio

Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.

DOI: 10.4236/jct.2013.43085                

Abstract

Several recent studies in mCRPC have identified the mechanisms of tumoral growth after the disease becomes unresponsive to standard hormonal therapy. These studies have highlighted the importance of residual intratumoral androgens in maintaining androgen receptor (AR) transcriptional activity in mCRPC [1]. Based on this findings, it has been possible to develop drugs, blocking the key enzyme in the biosynthesis of androgens through the inhibition of cytochrome p450 17 (CYP17) such as Abiraterone Acetate (AA) and drugs which directly target the AR including Enzalutamide (E) and Orteronel. Before this new knowledge, mCRPC treatment benefited from chemotherapy with taxanes. Recently a new taxane, Cabazitaxel (C), was approved in second line setting in association with prednisone. Retrospective analyses have tried to clarify the current role of chemotherapy in mCRPC patients and the right chemotherapy sequence of use of chemotherapy compared to new hormonal agents. Moreover, it would be important to address changes in the endpoints used in clinical trials, based on the stage of disease including the presence tumor-related symptoms, in order to identify the right therapeutic strategy.

Keywords

Metastatic Castration Resistant Prostate Cancer; Abiraterone; Cabazitaxel; Enzalutamide

Conflicts of Interest

The authors declare no conflicts of interest.

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