Activity of ketoconazole after taxane-based chemotherapy in castration-resistant prostate cancer

BJU Int. 2010 May;105(10):1392-6. doi: 10.1111/j.1464-410X.2009.08971.x. Epub 2009 Oct 23.

Abstract

Objective: To assess the efficacy of the androgen-synthesis inhibitor ketoconazole as a secondary hormonal therapy in patients with castration-resistant prostate cancer (CRPC) previously treated with chemotherapy, as persistent androgens appear to play a role in the development and maintenance of CRPC.

Patients and methods: We retrospectively identified 34 patients with CRPC who were treated with ketoconazole as a secondary hormonal therapy after paclitaxel- or docetaxel-based chemotherapy for CRPC. They were treated with ketoconazole 200-400 mg three times daily with or without hydrocortisone. Patients with previous use of ketoconazole were excluded. Half the patients had received estramustine as part of their chemotherapy regimen. The primary endpoint was the proportion of patients with a decline of > or =50% in their prostate-specific antigen (PSA) level. PSA progression was defined by the PSA Working Group 1 Criteria.

Results: Eight of the 32 evaluable patients (25%) had a PSA decline of > or =50%. The median time to progression (TTP) was 3 months (95% confidence interval, 1.2-5.4). A history of previous response to taxane-based chemotherapy was not associated with the response to ketoconazole. However, previous use of oestrogens for CRPC was significantly associated with a shorter TTP on ketoconazole (1.5 vs 10.2 months; P = 0.03).

Conclusions: Ketoconazole has moderate activity as secondary hormonal therapy in patients with CRPC previously treated with taxane-based chemotherapy, although the TTP was short. Previous treatment with oestrogenic therapy is associated with a shorter TTP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Androgen Antagonists / therapeutic use*
  • Antineoplastic Agents, Hormonal / therapeutic use*
  • Bridged-Ring Compounds / therapeutic use*
  • Castration
  • Disease Progression
  • Humans
  • Ketoconazole / therapeutic use*
  • Male
  • Middle Aged
  • Orchiectomy
  • Prostate-Specific Antigen / metabolism*
  • Prostatic Neoplasms / blood
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / surgery
  • Retrospective Studies
  • Taxoids / therapeutic use*
  • Time Factors
  • Treatment Outcome

Substances

  • Androgen Antagonists
  • Antineoplastic Agents, Hormonal
  • Bridged-Ring Compounds
  • Taxoids
  • taxane
  • Prostate-Specific Antigen
  • Ketoconazole