Critical appraisal of cabazitaxel in the management of advanced prostate cancer

Clin Interv Aging. 2010 Dec 3:5:395-402. doi: 10.2147/CIA.S14570.

Abstract

Docetaxel remains a cornerstone of therapy for the patient with metastatic castration-resistant prostate cancer (CRPC). However, the landscape of CRPC therapy is changing rapidly - recently, data from the phase III TROPIC study revealed a survival advantage with the novel taxane cabazitaxel/prednisone (compared with mitoxantrone/prednisone) in a cohort of 755 men with docetaxel-refractory metastatic CRPC. Interestingly, cabazitaxel bears substantial structural similiarity to docetaxel but appears to be mechanistically distinct. In preclinical studies, the agent has antitumor activity in a variety of docetaxel-refractory in vitro and in vivo models. Subsequent to phase I testing in advanced solid tumors (where neutropenia was identified as a dose-limiting toxicity), the agent was assessed in a phase II trial in advanced, taxane-refractory breast cancer and in the aforementioned phase III TROPIC study. This review describes in detail the preclinical and clinical development of cabazitaxel.

Keywords: Jevtana; breast cancer; cabazitaxel; castration resistant prostate cancer; taxane.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Breast Neoplasms / drug therapy
  • Clinical Trials, Phase I as Topic
  • Clinical Trials, Phase II as Topic
  • Clinical Trials, Phase III as Topic
  • Docetaxel
  • Drug Resistance, Neoplasm
  • Female
  • Humans
  • Male
  • Mice
  • Neutropenia / chemically induced
  • Prednisone / therapeutic use
  • Prostatic Neoplasms / drug therapy*
  • Rats
  • Taxoids / adverse effects
  • Taxoids / chemistry
  • Taxoids / pharmacology
  • Taxoids / therapeutic use*

Substances

  • Antineoplastic Agents
  • Taxoids
  • Docetaxel
  • cabazitaxel
  • Prednisone