Phase I study of non-pegylated liposomal doxorubicin in combination with ifosfamide in adult patients with metastatic soft tissue sarcomas

Objective The aim of this study was to evaluate the maximum tolerated dose (MTD) and safety of the combination of non- pegylated liposomal doxorubicin (Myocet) and ifosfamide in patients with metastatic soft tissue sarcomas. Methods Cohorts of four patients with metastatic soft tissue sarcomas received up to five cycles of intravenous ifosfamide 3000 mg/m2 on days 1– 3 in combination with escalating doses of intravenous Myocet on day 1 every 3 weeks until dose limiting toxicity (DLT) in at least one patient. Starting dose of Myocet was 40 mg/m2 to be escalated through 10 mg/m2 increase up to 80 mg/m2. Toxicity was graded according to the National Cancer Institute Common Toxicity Criteria v3.0 (NCI-CTC v3.0). Results Ten patients were enrolled in the study and 8 of them received the treatment. Median age was 45 years, 3 patients were male and 5 were female. DLT, consisting of neutropenic fever, was reached in one patient at dose level 2 (Myocet 50 mg/m2). Therefore, the MTD and the recommended phase II dose is 40 mg/m2. Conclusions The combination of intravenous Myocet 40 mg/m2 on day 1 and ifosfamide 3,000 mg/m2 on days 1–3 every 3 weeks is safe and feasible; a phase II study is ongoing.