Common practice is to treat men with advanced prostate cancer with androgen inhibition therapy (ADT) with or without antiandrogens (Casodex). Most of our prostate cancer will progress and develop into androgen-independent prostate cancer despite our achieving castrate testosterone levels.

Dutasteride, a 5-alfa-reductase inhibitor, is commonly used in the treatment of benign prostatic hyperplasia (BPH). Additional, despite the controversy around its use, some physicians use it as a third drug along with ADT2, ADT3.

Recently a prospective study was reported that evaluated the clinical utility of using dutasteride, in the treatment of hormone refractory prostate cancer. In this study 8 men who were hormone refractory were evaluated prospectively. After antiandrogen withdrawal and then after experiencing the expected increase in PSA, 5 of the men patients were given docetaxel plus prednisone and 3 of them received ketoconazole plus hydrocortisone. Additional all 8 of them were given 2 tablets of 0.5 mg of dutasteride.

The researchers defined a positive therapeutic response as a >50% reduction in PSA or a 75% reduction of PSA at 4 weeks after the start of combined protocol. The mean duration of the study follow-up was 9 months with a range of 21-24 months. A reduction >50% or >75% in PSA (positive therapeutic response as defined by the researcher) was noted in 4 and 6 patients, respectively. Bone scans detected no normalization of bone lesions (healing); computed tomography scanning showed no partial response to treatment. The mean duration of the PSA response was 6.9 months with a range of 0-21 months. Two (25%) of the 8 patients died at 6 and 10 months, respectively, neither of which had responded to the use of dutasteride. Only 1/8 patients reported experiencing dyspepsia (indigestion and chronic pain in the upper abdomen).

The researchers concluded that the data support the use of dutasteride in the treatment of hormone refractory prostate cancer. The claimed the study findings show that dutasteride is useful in the treatment of hormone refractory prostate cancer.

A careful reading of the data does not actually support their conclusions. First, their sample size is too small to allow any broad sweeping conclusions to be made about the use of dutasteride in the general population. Secondly, if you accept the data the only evidence this study gives us is that PSA scores are affected by the introduction of the dutasteride. This is no different from the current argument we have about the use of all the 5-alfa-reductase drugs in early prostate cancer treatment. There was no evidence of any slowing of disease progression or extension of life, the critical factors that we need to know about.

The use of PSA as a biomarker is significantly flawed (see my other PSA related posts). We cannot assume that a lowering of the PSA has any positive effect on disease progression, quality of life or eventual survival time.

Minerva Urol Nefrol. 2008 Jun;60(2):71-76.

PubMed Abstract

Joel T Nowak, MA, MSW