An open-label, single-arm phase two trial of gefitinib in patients with advanced or metastatic castration-resistant prostate cancer

OBJECTIVE: To determine whether the oral epidermal growth factor receptor (EGFR) inhibitor gefitinib (ZD1839, Iressa®) has clinical efficacy in patients with castration-resistant prostate cancer (CRPC). METHODS: Multicenter open-label phase 2 study. Fifty-one male patients with CRPC and rising PSA levels were enrolled to obtain the target enrollment of 38 patients who completed at least 3 months of treatment with continuous gefitinib 500 mg/d. The primary end point was the prostate-specific antigen (PSA) response rate, as defined by a confirmed 50% decline in serum PSA. RESULTS: One patient had a confirmed PSA response, giving a response rate of 2.0% (95% CI 0.1-10.4%). The median time to progression was 28 days and the median time on study was 85 days. The majority of patients had a stable performance status while on study. Of the 51 patients who received at least 1 dose of gefitinib, 13 patients had a dose reduction and 9 patients withdrew because of an adverse event. CONCLUSIONS: There was minimal evidence of single-agent gefitinib activity in CRPC. The treatment was associated with clinically relevant toxicities, which responded to dose interruption or reduction.