Pharmacotherapeutic strategies for castrate-resistant prostate cancer

ABSTRACT

Introduction

Metastatic castration-resistant prostate cancer (CRPC) is a potentially symptomatic disease with an eventual lethal outcome. Novel pharmaceutical agents are continuously studied with encouraging results in CRPC.

Areas covered

In this perspective, the authors present established and promising pharmacotherapeutic strategies for the management of CRPC; both with and without metastases. Apart from the different treatment strategies, the authors present the relevant sequence of treatment through disease progression.

Expert opinion

Usually, docetaxel should be considered the first line treatment in mCRPC. Abiraterone acetate (AA) plus prednisone or enzalutamide (ENZ) could be alternative treatments in chemotherapy naïve patients. Sipuleucel-T has been approved for the treatment of asymptomatic or minimally symptomatic mCRPC. Ra-223 has been approved for patients with mCRPC with symptomatic bone metastases (not visceral metastases). Cabazitaxel has been approved as the second line treatment to docetaxel in mCRPC. No differences in the overall survival has been observed between sequences starting with docetaxel versus AA/ENZ. Between AA-to-ENZ and ENZ-to-AA sequence, the AA-to-ENZ sequence appeared to be more favorable than the ENZ-to-AA regarding progression-free survival but not overall survival. Carbazitaxel seemed to retain its activity regardless of the treatment sequence. Of note, ENZ and apalutamide have been approved in non-metastatic CRPC.

KEYWORDS:

• Prostate cancer
• castration-resistant
• radium-223
• sipuleucel-T
• carbazitaxel
• apalutamide
• abiraterone Acetate
• enzalutamide

Article Highlights

• Metastatic castration-resistant prostate cancer (mCRPC) spreads quickly and does not respond to surgical or medical castration. It is defined as serum testosterone level <50 ng/dL

• Docetaxel is an anti-microtubular agent that belongs to the family of taxanes. It has been approved as the first line chemotherapeutic agent for the treatment of mCRPC

• Both abiraterone and enzalutamide improve the overall survival in men with mCRPC who are chemotherapeutically naïve and have previously been treated with docetaxel

• Sipuleucel-T is an effective treatment option for patients with early mCRPC

• Radium 223 is approved for the treatment of mCRPC patients with symptomatic bone metastasis but no visceral metastases

• Cabazitaxel represents a therapeutic option for men with metastatic CRPC whose condition has progressed with docetaxel treatment

• No consensus has been made regarding ideal sequence therapy for mCRPC, yet multiple combinations have been suggested.

• Immunotherapy clinical trials with immune checkpoint blockade therapies are currently revolutionizing the management of mCRPC

• Understanding the mechanism of resistance of each drug used for mCRPC can enable the development of novel-generation therapies

This box summarizes key points contained in the article.

Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.