Purpose: To establish the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), safety and recommended Phase II dose of ixabepilone, administered weekly as an intravenous (IV) infusion to patients with solid tumors who have failed standard therapy.
Method: This was an open-label, single-arm, Phase I, dose-escalation study.
Results: The MTD of ixabepilone [30-min, weekly IV infusion on a 21-day schedule (N = 33)] was established at 25 mg/m(2). Grade 3 fatigue was the DLT in 2/4 patients treated at 30 mg/m(2). Ixabepilone was well tolerated at the MTD. Myelosuppression was rare, with no Grade 3/4 neutropenia. Due to the potential for cumulative neurotoxicity, the protocol was amended to a 1-h infusion, weekly for 3 weeks with a 1-week break. No DLT occurred at starting doses of 15, 20 and 25 mg/m(2) on this modified schedule (N = 51), although overall toxicity was less at 15 and 20 mg/m(2) than 25 mg/m(2). Five patients (2 on the 30-min/21-day schedule and 3 on the 60-min/28-day schedule) achieved durable objective partial responses across a variety of tumor types.
Conclusions: Ixabepilone had an acceptable safety profile at the MTD of 25 mg/m(2) (as a 30-min weekly infusion on a continuous 21-day schedule) and at 20 mg/m(2) (as a 1-h weekly infusion on a modified 28-day schedule). The clinical activity and acceptable tolerability profile warrant further single- or combination-agent evaluation.