Phase II study of Dutasteride for recurrent prostate cancer during androgen deprivation therapy

J Urol. 2009 Feb;181(2):621-6. doi: 10.1016/j.juro.2008.10.014. Epub 2008 Dec 16.

Abstract

Purpose: We determined the response rate to and safety of a dual 5alpha-reductase inhibitor, dutasteride, in men with castration recurrent prostate cancer.

Materials and methods: A total of 28 men with asymptomatic castration recurrent prostate cancer were treated with 3.5 mg dutasteride daily (luteinizing hormone-releasing hormone treatment continued), and evaluated monthly for response and toxicity. Eligibility included appropriate duration antiandrogen withdrawal, baseline prostate specific antigen 2.0 ng/ml or greater and a new lesion on bone scan, increase in measurable disease using Response Evaluation Criteria in Solid Tumors criteria, or 2 or more consecutive prostate specific antigen measurements increased over baseline. Outcomes were progression, stable disease, partial response (prostate specific antigen less than 50% of enrollment for 4 or more weeks) or complete response.

Results: There were 25 evaluable men with a mean age of 70 years (range 57 to 88), a mean prostate specific antigen of 61.9 ng/ml (range 5.0 to 488.9) and mean Gleason score 8 (range 6 to 10), 15 of whom had bone metastases. Eight men had 10 grade 3 or higher adverse events using National Cancer Institute Common Terminology Criteria, all of which were judged to be unrelated to treatment. Of the 25 men 14 had disease progression by 2 months, 9 had stable (2.5, 3, 3, 4, 4, 5, 5, 8.5, 9 months) disease, 2 had a partial response and none had a complete response. Overall median time to progression was 1.87 months (range 1 to 10, 95% CI 1.15-3.91).

Conclusions: Dutasteride rarely produces biochemical responses in men with castration recurrent prostate cancer. However, further study is warranted given its favorable safety profile.

Publication types

  • Clinical Trial, Phase II
  • Research Support, N.I.H., Extramural

MeSH terms

  • 5-alpha Reductase Inhibitors*
  • Aged
  • Aged, 80 and over
  • Androgen Antagonists / adverse effects
  • Androgen Antagonists / therapeutic use
  • Azasteroids / administration & dosage*
  • Disease-Free Survival
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Drug Resistance
  • Dutasteride
  • Follow-Up Studies
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Recurrence, Local / mortality*
  • Neoplasm Recurrence, Local / pathology
  • Prostatectomy / adverse effects
  • Prostatectomy / methods
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / mortality
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / surgery
  • Risk Assessment
  • Survival Analysis
  • Treatment Outcome

Substances

  • 5-alpha Reductase Inhibitors
  • Androgen Antagonists
  • Azasteroids
  • Dutasteride