Phase III randomized, intergroup trial assessing imatinib mesylate at two dose levels in patients with unresectable or metastatic gastrointestinal stromal tumors expressing the kit receptor tyrosine kinase: S0033

Blanke, C. D., Rankin, C., Demetri, G. D., Ryan, C. W., von Mehren, M., Benjamin, R. S., Raymond, A. K., Bramwell, V. H., Baker, L. H., Maki, R. G., Tanaka, M., Hecht, J. R., Heinrich, M. C., Fletcher, C. D., Crowley, J. J., Borden, E. C. (February 2008) Phase III randomized, intergroup trial assessing imatinib mesylate at two dose levels in patients with unresectable or metastatic gastrointestinal stromal tumors expressing the kit receptor tyrosine kinase: S0033. J Clin Oncol, 26 (4). pp. 626-32. ISSN 1527-7755 (Electronic)0732-183X (Linking)

URL: https://www.ncbi.nlm.nih.gov/pubmed/18235122
DOI: 10.1200/JCO.2007.13.4452

Abstract

PURPOSE: To assess potential differences in progression-free or overall survival when imatinib mesylate is administered to patients with incurable gastrointestinal stromal tumors (GIST) at a standard dose (400 mg daily) versus a high dose (400 mg twice daily). PATIENTS AND METHODS: Patients with metastatic or surgically unresectable GIST were eligible for this phase III open-label clinical trial. At registration, patients were randomly assigned to either standard or high-dose imatinib, with close interval follow-up. If objective progression occurred by Response Evaluation Criteria in Solid Tumors, patients on the standard-dose arm could reregister to the trial and receive the high-dose imatinib regimen. RESULTS: Seven hundred forty-six patients with advanced GIST from 148 centers across the United States and Canada were enrolled onto this trial in 9 months. With a median follow-up of 4.5 years, median progression-free survival was 18 months for patients on the standard-dose arm, and 20 months for those receiving high-dose imatinib. Median overall survival was 55 and 51 months, respectively. There were no statistically significant differences in objective response rates, progression-free survival, or overall survival. After progression on standard-dose imatinib, 33% of patients who crossed over to the high-dose imatinib regimen achieved either an objective response or stable disease. There were more grade 3, 4, and 5 toxicities noted on the high-dose imatinib arm. CONCLUSION: This trial confirms the effectiveness of imatinib as primary systemic therapy for patients with incurable GIST but did not show any advantage to higher dose treatment. It appears reasonable to initiate therapy with 400 mg daily and to consider dose escalation on progression of disease.

Item Type: Paper
Uncontrolled Keywords: Adult Aged Aged, 80 and over Benzamides Disease-Free Survival Female Follow-Up Studies Gastrointestinal Stromal Tumors/*drug therapy/genetics/*mortality/pathology Humans Imatinib Mesylate Male Middle Aged Piperazines/*administration & dosage Prognosis Proto-Oncogene Proteins c-kit/metabolism Pyrimidines/*administration & dosage Retrospective Studies Survival Rate
Subjects: diseases & disorders > cancer > drugs and therapies
diseases & disorders > cancer > cancer types > gastrointestinal stromal tumors
diseases & disorders > cancer > prognosis
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > kinase > tyrosine kinase
CSHL Authors:
Communities: CSHL labs > Maki lab
Depositing User: Matt Covey
Date: 1 February 2008
Date Deposited: 26 Oct 2016 18:42
Last Modified: 26 Oct 2016 18:42
Related URLs:
URI: http://repository.cshl.edu/id/eprint/33683

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