Activity of dutasteride plus ketoconazole in castration-refractory prostate cancer after progression on ketoconazole alone

Clin Genitourin Cancer. 2009 Oct;7(3):E90-2. doi: 10.3816/CGC.2009.n.030.


Background: Ketoconazole is a commonly used secondary hormonal therapy in castration-refractory prostate cancer (CRPC), but disease progression inevitably occurs. Both prostatic and metastatic lesions in patients with CRPC overexpress 5-alpha reductase (SRDA5) type I. We hypothesized that SRDA5 inhibition in combination with ketoconazole would mitigate progression after treatment with ketoconazole alone.

Patients and methods: A total of 10 patients with CRPC with progression after ketoconazole treatment were treated with a combination of ketoconazole plus dutasteride 0.5 mg/day, a dual SRDA5 inhibitor.

Results: After dutasteride addition, 8 (80%) of the 10 patients had varying degrees of prostate-specific antigen (PSA) decline relative to baseline. Median progression-free survival after dutasteride addition was 4.9 months (range, 2.7+ to 9.8 months); no patient had a >OR= 50% PSA decline.

Conclusion: We conclude that dutasteride added to ketoconazole at the time progression might prolong time to PSA progression in patients with CRPC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antineoplastic Agents, Hormonal / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Azasteroids / pharmacokinetics
  • Azasteroids / therapeutic use*
  • Biomarkers, Tumor / metabolism
  • Disease Progression
  • Dutasteride
  • Humans
  • Ketoconazole / pharmacokinetics
  • Ketoconazole / therapeutic use
  • Male
  • Middle Aged
  • Orchiectomy
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / surgery


  • Antineoplastic Agents, Hormonal
  • Azasteroids
  • Biomarkers, Tumor
  • Dutasteride
  • Ketoconazole