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High Dose Ketoconazole Shows Promise in Hormone-Refractory Prostate Cancer: Presented at ICACT

By Adrian Burton
Special to DG News

PARIS, FRANCE -- February 2, 2003 -- A phase II study has shown that high doses of ketoconazole might be an effective second line treatment for hormone-refractory prostate cancer.

Ketoconazole causes complete androgenic deprivation, blocking the production of both testosterone and suprarenal androgens.

During the 1980s it was tested for the prevention of alopecia, explained Dr. Adelaida Garcia Velasco, resident physician at Universidad Doce de Octubre, Madrid, Spain who presented the findings here February 1^st at the International Congress on Anti-Cancer Therapy. These early studies also showed, however, that it reduced prostate specific antigen (PSA) values in patients with prostate cancer.

The first studies to evaluate ketoconazole in the treatment of prostate cancer used very high doses that were not well controlled, and the drug appeared to be poorly tolerated, Dr. Garcia Velasco explained.

"We now know, however, that it is not that toxic," she added. "We wanted to know what kind of dose would be appropriate in the second line setting."

In this study, 40 patients with a median age of 71 years (range 53-84), who had failed a median of three previous therapies, were assigned to receive either a low dose of 600 mg/day or a high dose of 1200/day until disease progression.

Median PSA score at baseline was 103ng/mL and median performance status was 90%.

The researchers tested the efficacy of each dose by measuring the change in PSA levels. A response was defined as a greater than 50% reduction in score, followed by its confirmation four weeks later. Progression was defined as objective disease progression or a PSA increase greater than 50% above nadir or 25% over baseline.

Nineteen patients were evaluable in each dose group. PSA response rate was 47% for the high dose group and 26% in the low dose group (p=0.2). Median time to disease progression was much better in the high dose group -- 18 weeks compared to 11 weeks, respectively (p<0.035). After 40 weeks of follow-up, 6 patients remained responsive.

Toxicity was mostly mild in both dose groups, although 8.3% of all patients discontinued treatment because of gastrointestinal side effects. No hepatic toxicity was recorded.

"Ketoconazole seems to be tolerated very well and should be [a treatment option] to bear in mind for patients who have failed on other anti-hormone therapies, and for those who are not able or do not wish [to have] chemotherapy," said Dr. Garcia Velasco. "Given the better results seen with the high dose treatment, 1200mg/day should be given if possible."

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