Purpose-We determined the response rate to and safety of a dual 5α-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). Dutasteride is well tolerated and safe in men with lower urinary tract symptoms but its safety in men with castration recurrent prostate cancer remains unclear. 5 In this study we determined the safety of and response rate to dutasteride in men with castration recurrent prostate cancer.
Conclusions-Dutasteride
MATERIALS AND METHODSA total of 28 men with asymptomatic prostate cancer progression despite medical (LHRH agonist with or without antiandrogen) or surgical castration were enrolled in an institutional review board approved phase II study. The Prostate Specific Antigen Working Group definition of progressive disease was used for eligibility, that is 1) increased size of measurable lesions on radiographic study using RECIST, 2) new lesion on bone scan, or 3) 2 successive increases in PSA measured at least 1 week apart.6 , 7 No minimum increase in PSA was required. Other eligibility criteria included serum PSA 2.0 ng/ml or greater, appropriate duration of antiandrogen cessation (28 days or greater for flutamide, 42 days or greater for biclutamide or nilutamide), and Eastern Cooperative Oncology Group performance status 2 or less. PSA doubling time was calculated using 3 or more values.Dutasteride was administered daily at 3.5 mg until intolerable toxicity or evidence of disease progression. All patients were monitored with physical examinations and laboratory studies which included serum PSA at the initiation of therapy and every 4 weeks thereafter. Toxicity was graded using the NCI Common...
