Clinical implications for a treatment algorithm and differential indication to hormone therapy and chemotherapy options in metastatic castrate-resistant prostate cancer: a personal view

Abstract

Although docetaxel is still considered a mainstay of treatment in metastatic castrate-resistant prostate cancer (mCRPC), in the last few years, new agents have been developed to improve survival in this setting and reach a possible optimal personalized treatment strategy. In this paper, we provide a personal view and an algorithm for mCRPC patients, according to available evidence, personal opinion and experience. Abiratone acetate, cabazitaxel, radium-223, sipuleucel-T and enzalutamide, together with docetaxel, have demonstrated a survival benefit in these patients. The use of rechallenge with docetaxel in mCRPC patients with disease progression after a first response has been considered. These new agents complicated the scenario and posed the challenge to move from the old sequential to a new algorithm-based approach. At this stage, the algorithm is necessarily based on experts’ opinion, since the efficacy of a single agent in a specific setting has not been validated by sequential trials.

Keywords::

• abiraterone acetate
• androgen-deprivation therapy
• cabazitaxel
• castration-resistant prostate cancer
• docetaxel
• enzalutamide
• radium-223
• treatment algorithm

Financial & competing interests disclosure

This work is based on the presentations given at the third international meeting, ‘The Oncologist Meets the Patologist’ (Arezzo, Italy, 21 May 2013). This meeting was organized by the Department of Oncology, USL-8, Istituto Toscano Tumori, Ospedale San Donato, Arezzo, Italy, and was supported by Accademia Nazionale di Medicina. The authors wish to thank all the participants for their contribution to the meeting. Sergio Bracarda was an advisory board member for Janssen, Sanofi, Astellas, Genentech, Exelixis, Pfizer, Novartis and Glaxo Smith Kline. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Editorial assistance for the preparation of this manuscript was provided by Luca Giacomelli, Elisa Sala and Silvana Pileggi; this assistance was supported by Accademia Nazionale di Medicina.

Key issues

• Docetaxel is an effective treatment option in a majority of the patients with metastatic castrate-resistant prostate cancer. However, even patients who initially respond ultimately develop resistance.

• Novel anticancer agents, including abiraterone acetate, cabazitaxel, radium-223 and enzalutamide, have been approved for metastatic castrate-resistant prostate cancer progressing after docetaxel, and they have been recently shown to be active (except for cabazitaxel) also in the pre-docetaxel setting.

• The combination of some therapeutic options currently available would contribute to personalize the therapeutic strategy and improve outcomes.

• The dentification of predictor markers for efficacy is required to fully benefit from these novel agents.

Notes