Randomized phase II study of trabectedin (ET-743) given by two different dosing schedules in patients (pts) with leiomyosarcomas (LMS) or liposarcomas (LPS) refractory to conventional doxorubicin and ifosfamide chemotherapy

9000 Background: Trabectedin (Yondelis), a marine-derived alkaloid, has shown antitumor activity as therapy for advanced STS in pts refractory to conventional chemotherapy. LMS and LPS pts were selected for further study since these subtypes appeared to have somewhat higher rates of clinical benefit than other STS subtypes. Methods: To evaluate the efficacy and tolerability of ET-743 administered either as a 3-hr IV infusion given weekly for 3 consecutive weeks in a 4 week cycle (Arm A) or as a 24-hr IV infusion q 3 weeks (Arm B) to pts following progression despite prior doxorubicin plus ifosfamide chemotherapy. Pts with PS 0–1, normal bilirubin and alkaline phosphatase (AP) levels, and measurable LMS or LPS were eligible for study. Patients were pretreated with dexamethasone.The ET-743 dose was reduced if any abnormal elevation of bilirubin or AP was noted between cycles, or if any other unacceptable toxicity occurred. Histology will be centrally reviewed and patients whose diagnosis cannot be confirmed...