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

• Published in: The Journal of urology Vol. 181; no. 2; p. 621
• Main Authors: Shah, Satyan K, Trump, Donald L, Sartor, Oliver, Tan, Wei, Wilding, Gregory E, Mohler, James L
• Format: Journal Article
• Language: English
• Published: United States 01-02-2009
• Subjects: 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
• ISSN: 1527-3792
• DOI: 10.1016/j.juro.2008.10.014

We determined the response rate to and safety of a dual 5alpha-reductase inhibitor, dutasteride, in men with castration recurrent prostate cancer.
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.
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 rarely produces biochemical responses in men with castration recurrent prostate cancer. However, further study is warranted given its favorable safety profile.