Ketoconazole retains activity in patients with docetaxel-refractory prostate cancer.

Preclinical and clinical data support the importance of signaling via the androgen receptor even in the setting of castration-resistant prostate cancer. However, the role of additional hormonal manipulations in patients progressing on cytotoxic chemotherapy has not been well defined. Recently, the novel lyase inhibitor, abiraterone acetate, has shown activity in patients with docetaxel-refractory disease [1, 2]. The activity of ketoconazole in this clinical state has not previously been described. We carried out an institutional review boardapproved retrospective review to evaluate the activity of ketoconazole in patients with castration-resistant metastatic prostate cancer who had progressed while on prior treatment with docetaxel. Patients treated from 1 January 2005 to 6 June 2008 were identified through record reviews. Eleven patients (median age = 73 years) were identified with characteristics detailed in Table 1. None of the patients had received ketoconazole before docetaxel. The median number of cytotoxic regimens administered before ketoconazole was 1 (range 1–3). With ketoconazole treatment, 4 of 11 (36%; 95% confidence interval 8% to 65%) patients achieved a ‡50% post-treatment decline in prostate-specific antigen (PSA) including three of four patients who did not achieve a ‡50% PSA decline with prior docetaxel and three of four patients treated with ketoconazole without steroids. Reasons for discontinuation of ketoconazole included progression in five patients and toxicity in one patient; five patients remain on treatment. Based on this small retrospective analysis, the inhibitor of adrenal androgen synthesis, ketoconazole, retains activity in patients with docetaxel-refractory prostate cancer. This readily accessible agent could be considered for treatment Annals of Oncology letters to the editor