title: Outcome of patients with advanced gastro-intestinal stromal tumours crossing over to a daily imatinib dose of 800 mg after progression on 400 mg.
abstract: In the EORTC-ISG-AGITG trial 946 patients with advanced gastro-intestinal stromal tumours (GIST) were randomised to receive 400 or 800 mg of imatinib daily. An increase in progression free survival (PFS) was demonstrated for patients randomised to the high-dose arm. Patients randomised to low-dose could cross-over to high-dose upon progression. We evaluated the feasibility, safety and efficacy of this policy. Of the 241 patients available for follow-up, 133 patients (55%) crossed over to high-dose imatinib according to the protocol. Of these patients, 92% had not had a prior dose reduction. The cumulative incidence of subsequent dose reductions after cross-over was 17% after six months with 51% discontinuing therapy without requiring a dose reduction. The extent of anaemia and fatigue increased significantly after cross-over, whilst neutropenia was less severe than during low-dose treatment. Objective responses after cross-over included three patients (2%) with a partial response and 36 (27%) with stable disease. The median PFS after cross-over was 81 days, although 18.1% of patients were still alive and progression free one year after cross-over. We conclude that a cross-over to high-dose imatinib is feasible and safe in GIST patients who progress on low-dose therapy.
authors.affiliation: Department of Medical Oncology, Division of Haematology and Medical Oncology, Peter MacCallum Cancer Centre, Locked Bag 1, A'Beckett Street, Melbourne, Vic. 8006, Australia. john.zalcberg@petermac.org
authors.forename: John R
authors.initials: JR
authors.lastname: Zalcberg
authors.forename: Jaap
authors.initials: J
authors.lastname: Verweij
authors.forename: Paolo G
authors.initials: PG
authors.lastname: Casali
authors.forename: Axel
authors.initials: A
authors.lastname: Le Cesne
authors.forename: Peter
authors.initials: P
authors.lastname: Reichardt
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Blay
authors.forename: Marcus
authors.initials: M
authors.lastname: Schlemmer
authors.forename: Martine
authors.initials: M
authors.lastname: Van Glabbeke
authors.forename: Michelle
authors.initials: M
authors.lastname: Brown
authors.forename: Ian R
authors.initials: IR
authors.lastname: Judson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001549:Benzamides; D018592:Cross-Over Studies; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D005240:Feasibility Studies; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy*; D006801:Humans; D000068877:Imatinib Mesylate; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage*; D011743:Pyrimidines / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate