Novel chemotherapies in development for management of castration-resistant prostate cancer

Curr Opin Urol. 2013 May;23(3):220-9. doi: 10.1097/MOU.0b013e32835f7da2.

Abstract

Purpose of review: Four new therapies have been recently approved for the treatment of men with castration-resistant prostate cancer; still, more treatment options are needed. This review summarizes the data supporting a role for novel chemotherapies including epothilones and immunomodulators (IMiDs), as well as other novel agents within the new landscape of approved therapies.

Recent findings: Epothilones are a class of chemotherapy that target microtubule disassembly, similar to taxanes. Results from phase II studies demonstrating a positive impact on serum prostate-specific antigen for patupilone and sagopilone, current epothilones in development, along with those of ixabepilone, are comparable with historical response rates to docetaxel, the current first-line chemotherapy for castration-resistant disease. IMiDs, including lenalidamide and thalidomide, are also in active development in castration-resistant prostate cancer. A recent phase III study evaluating the combination of lenalidomide and docetaxel revealed decreased overall survival relative to docetaxel alone; however, additional trials are currently recruiting to investigate lenalidomide in various other combination regimens.

Summary: Epothilones could be efficacious as an additional therapy in patients who respond to docetaxel chemotherapy. A role for IMiDs, perhaps in combination with chemotherapy or androgen pathway inhibitors, remains to be elucidated.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Androgen Antagonists / therapeutic use*
  • Animals
  • Antineoplastic Agents, Hormonal / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Drug Design
  • Drug Resistance, Neoplasm*
  • Epothilones / therapeutic use
  • Humans
  • Immunologic Factors / therapeutic use
  • Immunotherapy / methods
  • Male
  • Microtubules / drug effects
  • Neoplasms, Hormone-Dependent / drug therapy*
  • Neoplasms, Hormone-Dependent / immunology
  • Neoplasms, Hormone-Dependent / metabolism
  • Neoplasms, Hormone-Dependent / surgery
  • Orchiectomy*
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / immunology
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / surgery
  • Receptors, Androgen / drug effects
  • Receptors, Androgen / metabolism
  • Signal Transduction / drug effects
  • Treatment Outcome
  • Tubulin Modulators / therapeutic use
  • Tumor Microenvironment / drug effects

Substances

  • Androgen Antagonists
  • Antineoplastic Agents, Hormonal
  • Epothilones
  • Immunologic Factors
  • Receptors, Androgen
  • Tubulin Modulators