A phase II study of ET-743/trabectedin (`Yondelis') for patients with advanced gastrointestinal stromal tumours

• Published in: European journal of cancer (1990) Vol. 40; no. 9; pp. 1327 - 1331
• Main Authors: Blay, J.-Y., Le Cesne, A., Verweij, J., Scurr, M., Seynaeve, C., Bonvalot, S., Hogendoorn, P., Jimeno, J., Evrard, V., van Glabbeke, M., Judson, I.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01-06-2004; Elsevier
• Subjects: Adult; Aged; Antineoplastic Agents, Alkylating - therapeutic use; Biological and medical sciences; Dioxoles - therapeutic use; Female; Gastrointestinal Neoplasms - drug therapy; Gastrointestinal Neoplasms - mortality; Humans; Isoquinolines - therapeutic use; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Sarcoma - drug therapy; Sarcoma - mortality; Survival Rate; Tetrahydroisoquinolines; Treatment Failure; Tumors; Antineoplastic agent; Human; Cancerology; Phase II trial; Stroma; Tumor; Pharmacology; Gastrointestinal; Trabectedin
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2004.02.005

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 ⩾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.