At the University of New Mexico School of Medicine in Albuquerque, New Mexico (SKS) the Department of Urology just completed a study that showed that dutasteride, the generic name for a dual 5alpha-reductase inhibitor made by GlaxoSmithKline and marketed under the name Avodart™ in the US and Avolve™ in Europe, when administered to men with castration recurrent prostate cancer, they did not provide any clinical benefit. The use of dutasteride in this situation was safe as it had no toxic effects.
Dutasteride is used by some physicians as a third leg in hormone therapy (ADT3) for the treatment of prostate cancer. Its value is often debated in this treatment modality as there has not been any conclusive studies demonstrating its ability to extend life.
This study was designed as a phase II trial, so the actual goals of the study was to determined the response rate to and safety of dutasteride
The trial consisted of 28 men (small numbers as is typical of phase II trial) with asymptomatic castration recurrent prostate cancer who were treated with 3.5 mg dutasteride daily. All subjects continued to receive luteinizing hormone-releasing hormone treatment during the entire study. All the men were evaluated monthly for response and toxicity to the dutasteride.
To have been included into the trial all the men received the appropriate duration antiandrogen withdrawal, had a baseline prostate specific antigen (PSA) of 2.0 ng/ml or greater and had experienced 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.
The outcomes that were evaluated 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).
CONCLUSIONS: Dutasteride rarely produces biochemical responses in men with castration recurrent prostate cancer.
Keep in mind this was a small study and with a sample size of this number it is hard to draw exact conclusions. The other popular 5alpha-reductase inhibitor, Proscar, has similar clinical mechanism, but we can not draw automatic conclusions as to what the effect Proscar would have had in this study.
J Urol. 2008 Dec 15.