Low dose of ketoconazole in patients with prostate adenocarcinoma resistant to pharmacological castration

• To assess the efficacy of ketoconazole in patients with castration-resistant prostate cancer (CRPC).

• From April 2008 to November 2009, 37 patients with CRPC have been treated with ketoconazole. The primary endpoint was the prostate-specific antigen (PSA) response; the secondary endpoints were progression-free survival and safety profile. • Ketoconazole was administered by oral route at a dose of 200 mg every 8 h continuous dosing until the onset of serious adverse events or disease progression. • The study was based on a two-step design with an interim efficacy analysis carried out on the first 12 patients accrued.

• Main characteristics of population were: median age 75 years (range 60-88); baseline mean PSA 28.8 ng/mL (4.3-1000); 30 patients previously challenged with at least two lines of hormone therapy; 15 patients previously treated with chemotherapy. • Biochemical responses accounted for: two complete responses (5%), six partial responses (16%), 13 patients with stable disease (35%), and 14 with progressive disease (38%). Of 15 patients resistant to chemotherapy, overall disease control (complete plus partial responses plus stable disease) was recorded in seven of them. • Treatment was feasible without inducing grade 3-4 adverse events. The most common grade 1-2 adverse events were asthenia (27%), vomiting (8%) and abdominal pain (8%).

• Treatment with low-dose ketoconazole is feasible and well tolerated. The efficacy was satisfactory in patients previously treated with chemotherapy.