Efficacy of low-dose ketoconazole in hormone refractory prostate cancer patients (HRPC): A single institution experience

Abstract

16117 Background: The management of HRPC remains controversial. Among the options, second-line hormonal therapy is commonly used. Ketoconazole, an antimycotic which affects the synthesis of androgens and other steroids, has shown direct cytotoxic effects in prostate cancer. This study describes our experience with low-dose ketoconazole treatment for HRPC. Methods: All eligible pts had histologically proven adenocarcinoma of the prostate, and all pts had progressive castration resistant prostate cancer by consensus criteria and had received no prior hormonotherapy. Pts received 400 mg ketoconazole orally 3 times daily, and orally replacement hydrocortisone. PSA response was defined as a >50% fall in PSA from baseline, confirmed by a second PSA value 4 or > weeks later. Pts with measurable soft tissue disease met traditional guidelines for tumour responses. Progression was defined by objective disease progression or PSA increase of >50% above nadir or >25% above baseline. Pts were monitored clinically and with serial PSA measurements every 1 month. Results: Data for 73 pts were analysed. Median age was 73 years(57–89), median PSA was 67.8 ng/ml (range: 7.5–347.0), with a median performance status of 90%(range: 70–90%). Of the 70 pts (PSA data missing in 3 pts), 33 (47.0%) showed a decrease in PSA >50% (95% CI 37.5%-61.4%) with a median duration of 7.8 months (range 4–41 months). We observed objective responses in 12 of 34 pts(35%) with measurable soft tissue disease and bone metastasis. Age, PSA at diagnosis, Performance status, Gleason score and bone scan result were not significantly associated with response to ketoconazole treatment in univariate or multivariate analyses. A longer duration of primary androgen deprivation therapy (ADT) and total duration of previous hormonal therapy was associated with a longer time to progression.Toxicity was mild with 5 of 73 patients(7.0%) discontinued therapy because of gastrointestinal side-effects or moderate elevated transaminases. No acute hepatitis or adrenal insufficiency was observed. Conclusions: Low-dose Ketoconazol is an effective and well-tolerated treatment in pts with HRPC and should be considerate in a subset of pts with low-volume disease and a rising PSA level despite ADT. No significant financial relationships to disclose.