Ixabepilone, mitoxantrone, and prednisone in patients with metastatic castration-resistant prostate cancer refractory to docetaxel-based therapy: A phase II study of the DOD Prostate Cancer Clinical Trials Consortium

5058 Background: Mitoxantrone (M) plus prednisone (P) and ixabepilone (Ix) each have modest, non cross-resistant activity as second line chemotherapy regimens in docetaxel-refractory patients with CRPC. These agents were therefore combined in a phase I study which demonstrated anti-cancer activity and defined the recommended phase II dose used in this trial. Methods: Patients with metastatic CRPC and progression after 3 or more cycles of docetaxel were enrolled in a phase II multicenter study of the combination of prednisone 5 mg BID, Ix (35 mg/m2) and M (12 mg/m2) administered intravenously on day 1 every 21 days, with pegfilgrastim (6 mg on day 2) support. Results: To date, 43 pts have been enrolled and have received a median of 4 cycles. Of 37 patients currently evaluable for response, 14 (38%; 95% CI: 22–55%) have had a confirmed ≥50% decline in PSA and 19 (51%; 95% CI 34–68%) have had a confirmed ≥30% decline in PSA. Two of 15 patients with evaluable measurable disease (13%) have had a RECIST-defined objective response. All 43 patients are evaluable for toxicity. Grade 3 or 4 neutropenia was seen in 6 pts (17%) and grade 3 or 4 thrombocytopenia was seen in 3 (8%). Nonhematologic grade 3/4 events possibly related to study drug have included grade 3 fatigue (3 pts), grade 3 pneumonia (2 pts), and grade 3 atrial fibrillation, grade 4 myocardial infarction, grade 4 prostatitis, grade 3 nausea/vomiting, grade 3 neuropathy, grade 3 elevated transaminases, grade 3 dizziness, grade 3 dehydration, grade 3 shortness of breath, and grade 4 vasovagal syncope (1 pt each). Grade 2 neuropathy has been seen in 4 patients. Conclusions: The Ix, M, P regimen is active as second-line therapy in CRPC patients with progressive disease after docetaxel therapy and is reasonably well tolerated. Further investigation of this regimen is warranted. This study was supported in part by CTEP/NCI and the DOD Prostate Cancer Clinical Trials Consortium. [Table: see text]