Phase II clinical trial of the epothilone B analog, ixabepilone, in patients with non-small-cell lung cancer whose tumors have failed first-line platinum-based chemotherapy

Purpose: Ixabepilone is the first in a new class of antineoplastic agents, the epothilones and their analogs. This international, randomized, phase II trial assessed two administration schedules of ixabepilone as second-line therapy in patients with non-small-cell lung cancer (NSCLC). Patients and Methods: Patients had experienced disease progression after one prior cisplatin- or carboplatin-based chemotherapy regimen. Ixabepilone was administered as a single 32 mg/m² 3-hour infusion (77 patients; arm A) or a 6 mg/m ² 1-hour infusion daily for 5 consecutive days (69 patients; arm B) in a 3-week cycle. Results: The intent-to-treat objective response rate was 14.3% in arm A and 11.6% in arm B. Median duration of response was 8.7 months (95% CI, 5.3 to 9.5 months) in arm A and 9.6 months (95% CI, 6.1 to 19.7 months) in arm B. Median time to progression was 2.1 months (95% CI, 1.4 to 2.8 months) for arm A and 1.5 months (95% CI, 1.4 to 2.8 months) for arm B. Median survival was 8.3 months (95% CI, 5.8 to 11.5 months) for arm A, and 7.3 months (95% CI, 5.7 to 11.7 months) for arm B; the 1-year survival rate (both cohorts) was 38%. Responses occurred in patients with taxane-pretreated and platinum-refractory tumors. Both regimens had an acceptable toxicity profile. Myelosuppression was manageable, manifesting primarily as neutropenia and leukopenia. Neuropathy was primarily sensory, generally mild to moderate in severity, and mostly reversible (both regimens). Conclusion: Single-agent ixabepilone had clinically relevant activity and an acceptable safety profile in patients with advanced NSCLC whose tumors had failed one prior platinum-based chemotherapy regimen.