Phase II trial of liposomal doxorubicin (Doxil (R)) in advanced soft tissue sarcomas

Purpose: To assess the objective response rate, toxicity experienced, progr ession-free survival, and overall survival of patients with previously untr eated advanced soft tissue sarcomas treated with a liposomal doxorubicin fo rmulation (Doxil). Methods: Patients with metastatic or recurrent soft tissue sarcoma who had received no prior chemotherapy for advanced disease were treated with lipos omal doxorubicin (Doxil) according to a two stage accrual design. Doxil was administered at 50 mg/m(2) every 4 weeks. A total of 15 patients were trea ted and are evaluable for response and toxicity. Results: The male/female ratio was 7/8, the median age was 60 years (34-75) and the ECOG performance status was 0-1 in > 90% of patients. Leiomyosarco ma (7/15) and malignant fibrous histiocytoma (2/15) were the most common hi stologic diagnoses. No objective responses were observed in the 15 evaluabl e patients. No lethal toxicity occurred. Grade 3-4 leukopenia or neutropeni a were reported in 3/15 (20%) patients. Grade 3 mucositis or hand-foot synd rome occurred in 2/15 (13%) and 1/15 (7%) patients respectively and seemed more severe in older patients. The median time to progression was 1.9 month s (range 0.9-6.2). Twelve patients have now died. The Kaplan-Meier estimate of median overall survival is 12.3 months. As called for in the study desi gn, accrual was terminated because no responses were obtained in the first 15 patients. Conclusion: Though well-tolerated, Doxil given according to this dose and s chedule to patients with advanced soft tissue sarcoma had no significant th erapeutic activity. A correlation between older age and skin/mucosal toxici ty of Doxil is suggested in this study but needs confirmation. Future inves tigations of Doxil in soft tissue sarcomas should use a different schedule and dose.