Primary or secondary resistance to imatinib may occur in patients with gastrointestinal stromal tumours (GISTs) while these tumours have repeatedly been shown to be highly resistant to conventional doxorubicin- and ifosfamide-containing regimens. The investigation of new drugs is therefore warranted in GIST. A phase II study was conducted between May 1999 and November 2000 in eight centres of the EORTC STBSG group to establish the efficacy and safety of ET743 ('Yondelis') in GIST previously untreated with cytotoxic chemotherapy before the imatinib era. ET-743 was given was given at 1.5 mg/m(2) per course as a 24-h continuous intravenous infusion every 3 weeks. Twenty-eight patients were included, 16 males and 12 females. Median age was 54 years (range 25-73 years). Median performance status was 0 (range 0-1). 17 (63%), 4 (12%) and 7 (25%) patients, received 0-2, 3-5, and > or = 6 courses of ET-743, respectively. The best response was stable disease in 9 (33%) patients, and disease progression in 18 patients (67%), with a median time to disease progression and overall survival of 51 days and 589 days, respectively. The treatment was well tolerated: there were grades 3-4 neutropenia, thrombocytopenia, and transaminase increases in 13 (48%), 1 (4%) and 16 (59%) patients, respectively. There were no toxic deaths. ET-743 at this dose and schedule is not an effective treatment for advanced GIST.