Ecteinascidin-743: A marine-derived compound in advanced, pretreated sarcoma patients - Preliminary evidence of activity

Purpose: To report the activity of the chemotherapeutic agent ecteinascidin -743 (ET-743) in advanced pretreated sarcoma patients observed during a pha se I study and a named-patient basis, compassionate use program. Patients and Methods: Twenty-nine pretreated, advanced soft tissue sarcoma (STS) and bone sarcoma patients consecutively seen in our centers were incl uded, 12 from a phase I trial and 17 from a compassionate use program cohor t. patients were treated every 3 weeks at either 1,200 mug/m(2) (six patien ts), 1,500 mug/m(2) (the recommended dose, 22 patients), or 1,800 mug/m(2) (the maximum-tolerated dose, one patient), given as a 24-hour infusion ever y 3 to 4 weeks. Results: Fifteen men and 14 women were treated. The median patient age was 46 years (range, 16 to 71 years), with a median World Health Organization p erformance status of 1 (range, 0 to 2). Twenty-five patients had STS, three had osteosarcoma, and one had Ewing's sarcoma, and all had progressive dis ease at accrual. Fifteen patients herd bulky disease, and 14 had clinical r esistance to anthracyclines. A total of 136 treatment cycles were administe red (median per patient, five cycles; range, one to 12 cycles). Transient g rade 3 and 4 transaminitis was reported in 24% and 5% of cycles, respective ly, grade 3 to 4 neutropenia occurred in 32% of cycles, with concomitant sp oradic grade 3 to 4 thrombocytopenia in 5.1% of cycles. Grade 2 to 3 asthen ia occurred in 21% of cycles. There were two partial responses (PRs) in STS patients and two PRs in osteosarcoma patients. Two minor responses and 10 disease stabilizations were seen. Median duration of response was 10.5 mont hs (range, 2.8 to 15 months), and mean duration of stabilization was 5.2 mo nths. Conclusion: ET-743 has activity in advanced, highly pretreated STS and oste osarcoma patients and warrants further trials to establish the extent of if s activity in this setting. J Clin Oncol 19:1248-1255. (C) 2001 by American Society of Clinical Oncology.