Author:

Keywords:

gastrointestinal stromal tumour, gist, nilotinib, sunitinib, imatinib, tyrosine kinase inhibitor, compassionate use, chronic myelogenous leukemia, population-based incidence, endothelial growth-factor, bcr-abl, formerly amn107, dose imatinib, kit, mesylate, survival, Science & Technology, Life Sciences & Biomedicine, Oncology, Gastrointestinal stromal tumour, GIST, Nilotinib, Sunitinib, Imatinib, Tyrosine kinase inhibitor, Compassionate use, TYROSINE KINASE INHIBITOR, POPULATION-BASED INCIDENCE, ENDOTHELIAL GROWTH-FACTOR, FORMERLY AMN107, DOSE IMATINIB, MESYLATE, KIT, MUTATIONS, DIAGNOSIS, SURVIVAL, Adult, Aged, Aged, 80 and over, Antineoplastic Agents, Benzamides, Disease-Free Survival, Drug Resistance, Neoplasm, Female, Gastrointestinal Stromal Tumors, Humans, Imatinib Mesylate, Indoles, Male, Middle Aged, Patient Selection, Piperazines, Pyrimidines, Pyrroles, Retrospective Studies, Treatment Outcome, Young Adult, 1112 Oncology and Carcinogenesis, 1117 Public Health and Health Services, Oncology & Carcinogenesis, 3211 Oncology and carcinogenesis

Abstract:

Patients diagnosed with advanced gastrointestinal stromal tumours (GISTs) who are resistant or intolerant to both imatinib and second-line sunitinib have a poor prognosis and few therapeutic options. We evaluated the efficacy of nilotinib, a novel tyrosine kinase inhibitor (TKI) in patients pretreated with imatinib and sunitinib. Fifty-two consecutive patients treated with oral nilotinib, 400 mg twice daily, within the nilotinib compassionate use programme in 12 European cancer centres, were included in this retrospective analysis. Median age was 59 years (range 24-80), and all patients had WHO performance score better than 3. All patients had failed both imatinib and sunitinib pretreatment, either due to progressing GIST (96%) or intolerance (4%). Five patients (10%; 95% confidence interval (CI) 2-18) responded to nilotinib and 19 patients (37%; 95% CI 24-50) achieved a disease stabilisation. Nilotinib was generally well tolerated, but six patients (12%) discontinued treatment due to intolerance. Median progression-free survival of nilotinib treatment was 12 weeks (95% CI 9-15; range 0-104) and median overall survival was 34 weeks (95% CI 3-65; range 2-135). Nilotinib is active in GIST resistant to both imatinib and sunitinib. these results warrant further investigation of nilotinib in GIST. (C) 2009 Elsevier Ltd. All rights reserved.