Phase II trial of weekly patupilone in patients with castration-resistant prostate cancer

Background: Drug resistance mechanisms can reduce response rate and duration in men with castration-resistant prostate cancer (CRPC) receiving docetaxel-based therapy. Patupilone (epothilone B), a microtubule-targeting agent, may be unaffected by some resistance mechanisms. Therefore, a phase II study assessed the patupilone safety and activity in CRPC patients with and without previous chemotherapy. Methods: CRPC patients received patupilone 2.5 mg/m² weekly for 3 weeks of a 4-week cycle. Patients were required to have measurable disease or prostate-specific antigen (PSA) progression (levels > 20 ng/ml). Results: All 45 enrolled patients (median age, 69 years) were safety and response assessable. Sixty-four percent had previous chemotherapy (55% had previous taxane therapy). Patients received a median of three patupilone cycles. Patupilone was generally well tolerated. Ten (22%) patients experienced grade 3 diarrhea, six (13%) grade 3 fatigue, and one (2%) grade 3 neuropathy with no neutropenia or thrombocytopenia incidence. Six (13%) patients had ≥50% decline in PSA (three had previous taxane therapy). No patient with measurable disease had a response. Median overall survival was 13.4 months. Conclusions: The safety profile of weekly patupilone in CRPC patients compares favorably with that of other microtubule inhibitors. At the dose and schedule tested, patupilone demonstrated minimal activity in CRPC.