Dubbele dosis GLEEVEC verlengt tijd tot recidief van GIST

25 september 2004: Bron: Lancet 2004; 364: 1127-134

Nederlandse onderzoekers aan de Erasmus in Rotterdam hebben in samenwerking met veel ander buitenlandse onderzoekers en ziekenhuizen bewezen in een gerandomiseerde trial dat een dubbele dosis Gleevec bij GIST - Gastrointestinal Stromal Tumours - een zeldzame vorm van darmkanker, de tijd tot een recidief vergroot met 6%. Wat volgens de onderzoekers significant is. 99% van de patiënten ervaarden in beide groepen ernstige bijwerkingen. De studie werd vandaag gepubliceerd in The Lancet.

Progression-free survival in gastrointestinal stromal tumours with high-dose imatinib: randomised trial

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Lancet 2004; 364: 1127-134

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*Study investigators listed at end of report

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Department of Medical Oncology, Erasmus University Medical Centre, Groene Hilledijk 301, 3075 EA Rotterdam, Netherlands (Prof J Verweij MD); Department of Medical Oncology, Instituto Tumori, Milan, Italy (P G Casali MD, R Bertulli MD); Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia (Prof J Zalcberg MD); Department of Medical Oncology, Institute Gustave Roussy, Villejuif, France (A LeCesne MD); Department of Haematology, Oncology, and Tumorimmunology, HELIOS-Klinikum, Charite Campus Buch, Berlin, Germany (P Reichardt MD); Department of Medical Oncology, Centre L Berard INSERM U590 and Hospices Civils de Lyon, Lyon, France (Prof J-Y Blay MD); Department of Medical Oncology, Klinikum Grosshadern, Munich, and GSF-National Research Centre for Environment and Health, Neuherberg, Germany (Prof R Issels MD); Department of Oncology, University Hospital Gasthuisberg, Leuven, Belgium (Prof A van Oosterom MD); Department of Pathology, Leiden University Medical Centre, Leiden, Netherlands (Prof P C W Hogendoorn MD); EORTC Data Centre, Brussels, Belgium (M Van Glabbeke MSc); and Department of Medical Oncology, Royal Marsden Hospital, London, UK (Prof I Judson MD)

-------------------------------------------------------------------------------- Correspondence to: Prof Jaap Verweij j.verweij@erasmusmc.nl Jaap Verweij, Paolo G Casali, John Zalcberg, Axel LeCesne, Peter Reichardt, Jean-Yves Blay, Rolf Issels, Allan van Oosterom, Pancras C W Hogendoorn, Martine Van Glabbeke, Rossella Bertulli, Ian Judson, for the EORTC Soft Tissue and Bone Sarcoma Group, the Italian Sarcoma Group, and the Australasian Gastrointestinal Trials Group

* Summary

Background Imatinib is approved worldwide for use in gastrointestinal stromal tumours (GIST). We aimed to assess dose dependency of response and progression-free survival with imatinib for metastatic GIST.

Methods 946 patients were randomly allocated imatinib 400 mg either once or twice a day. Those assigned the once a day regimen who had progression were offered the option of crossover. The primary endpoint was progression-free survival. Analysis was by intention to treat.

Findings At median follow-up of 760 days (IQR 644-859), 263 (56%) of 473 patients allocated imatinib once a day had progressed compared with 235 (50%) of 473 who were assigned treatment twice a day (estimated hazard ratio 0·82 [95% CI 0·69-0·98]; p=0·026). Side-effects arose in 465/470 (99%) patients allocated the once daily regimen compared with 468/472 (99%) assigned treatment twice a day. By comparison with the group treated once a day, more dose reductions (77 [16%] vs 282 [60%]) and treatment interruptions (189 [40%] vs 302 [64%]) were recorded in patients allocated the twice daily regimen, but treatment in both arms was fairly well tolerated. 52 (5%) patients achieved a complete response, 442 (47%) a partial response, and 300 (32%) stable disease, with no difference between groups. Median time to best response was 107 days (IQR 58-172).

Interpretation If response induction is the only aim of treatment, a daily dose of 400 mg of imatinib is sufficient; however, a dose of 400 mg twice a day achieves significantly longer progression-free survival.