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

Mari Nakabayashi, William K. Oh, Susanna Jacobus, Meredith M. Regan, Mary Ellen Taplin, Philip W. Kantoff, Jonathan E. Rosenberg

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

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 ≥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 ≥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.

Original languageEnglish
Pages (from-to)1392-1396
Number of pages5
JournalBJU International
Volume105
Issue number10
DOIs
StatePublished - May 2010
Externally publishedYes

Keywords

  • Castration-resistant prostate cancer
  • Ketoconazole
  • PSA response
  • Secondary hormonal therapy
  • Taxane chemotherapy

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