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A phase II study of ET-743/trabectedin ('Yondelis') for patients with advanced gastrointestinal stromal tumours
J-Y Blay1, A Le Cesne, J Verweij
1Hop Edouard Herriot and INSERM U590 Centre Leon Berard, Lyon, France.
Abstract:
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.
Insights
This study found that ET-743 (Yondelis) is not an effective treatment for advanced gastrointestinal stromal tumors (GISTs) in patients not previously treated with chemotherapy. While generally well-tolerated, the drug did not demonstrate sufficient efficacy in this patient population.
Area of Science:
- Medical Oncology
- Clinical Pharmacology
- Gastrointestinal Oncology
Background:
- Gastrointestinal stromal tumors (GISTs) often develop resistance to imatinib and conventional chemotherapy.
- There is a need for novel therapeutic agents for advanced GISTs, particularly in the pre-targeted therapy era.
- ET-743 (Yondelis) is an antineoplastic agent investigated for various solid tumors.
Purpose of the Study:
- To evaluate the efficacy and safety of ET-743 in patients with advanced GIST.
- To determine the optimal dose and schedule for ET-743 in this patient population.
- To assess response rates, time to progression, and overall survival.
Main Methods:
- A Phase II clinical trial was conducted across eight centers.
- Twenty-eight patients with advanced GIST, untreated with cytotoxic chemotherapy, were enrolled.
- ET-743 was administered at 1.5 mg/m² every 3 weeks via continuous intravenous infusion over 24 hours.
Main Results:
- The best overall response was stable disease in 33% of patients; 67% experienced disease progression.
- Median time to disease progression was 51 days, and median overall survival was 589 days.
- The treatment was generally well-tolerated, with manageable toxicities including neutropenia and transaminase elevations, and no toxic deaths.
Conclusions:
- ET-743 at the tested dose and schedule demonstrated limited efficacy in advanced GIST patients.
- The drug's activity was insufficient to warrant further investigation in this specific setting.
- Further research into alternative therapeutic strategies for GIST is recommended.
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