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
- PMID: 18235122
- DOI: 10.1200/JCO.2007.13.4452
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
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.
Similar articles
-
A prospective, multicenter, phase 2 study of imatinib mesylate in korean patients with metastatic or unresectable gastrointestinal stromal tumor.Oncology. 2009;76(5):326-32. doi: 10.1159/000209384. Epub 2009 Mar 23. Oncology. 2009. PMID: 19307738 Clinical Trial.
-
Prospective multicentric randomized phase III study of imatinib in patients with advanced gastrointestinal stromal tumors comparing interruption versus continuation of treatment beyond 1 year: the French Sarcoma Group.J Clin Oncol. 2007 Mar 20;25(9):1107-13. doi: 10.1200/JCO.2006.09.0183. J Clin Oncol. 2007. PMID: 17369574 Clinical Trial.
-
Phase II study of oral masitinib mesilate in imatinib-naïve patients with locally advanced or metastatic gastro-intestinal stromal tumour (GIST).Eur J Cancer. 2010 May;46(8):1344-51. doi: 10.1016/j.ejca.2010.02.014. Epub 2010 Mar 6. Eur J Cancer. 2010. PMID: 20211560 Clinical Trial.
-
Optimizing the dose of imatinib for treatment of gastrointestinal stromal tumours: lessons from the phase 3 trials.Eur J Cancer. 2008 Mar;44(4):501-9. doi: 10.1016/j.ejca.2007.11.021. Epub 2008 Jan 29. Eur J Cancer. 2008. PMID: 18234488 Review.
-
The role of high-dose imatinib in the management of patients with gastrointestinal stromal tumor.Cancer. 2010 Apr 15;116(8):1847-58. doi: 10.1002/cncr.24944. Cancer. 2010. PMID: 20166214 Review.
Cited by
-
A case-matched study of imatinib mesylate between different formulations on plasma trough concentration, adverse events, quality of life and outcomes in gastrointestinal stromal tumor patients.PLoS One. 2024 May 14;19(5):e0303290. doi: 10.1371/journal.pone.0303290. eCollection 2024. PLoS One. 2024. PMID: 38743680 Free PMC article.
-
Safety outcomes of low versus high dose imatinib mesylate in patients with advanced, metastatic, or nonresectable gastrointestinal stromal tumors: A systematic review.Gastrointest Tract. 2024;2(1):10.54844/git.2023.482. doi: 10.54844/git.2023.482. Epub 2024 Mar 12. Gastrointest Tract. 2024. PMID: 38699682 Free PMC article.
-
Hemodialysis and imatinib: Plasma levels, efficacy and tolerability in a patient with metastatic GIST - Case report.Heliyon. 2024 Mar 27;10(7):e28494. doi: 10.1016/j.heliyon.2024.e28494. eCollection 2024 Apr 15. Heliyon. 2024. PMID: 38596050 Free PMC article.
-
Treatment Access for Gastrointestinal Stromal Tumor in Predominantly Low- and Middle-Income Countries.JAMA Netw Open. 2024 Apr 1;7(4):e244898. doi: 10.1001/jamanetworkopen.2024.4898. JAMA Netw Open. 2024. PMID: 38568688 Free PMC article.
-
Advancing the Management of Skull Base Chondrosarcomas: A Systematic Review of Targeted Therapies.J Pers Med. 2024 Feb 28;14(3):261. doi: 10.3390/jpm14030261. J Pers Med. 2024. PMID: 38541003 Free PMC article. Review.
Publication types
MeSH terms
Substances
Grants and funding
- A35178/PHS HHS/United States
- CA02599/CA/NCI NIH HHS/United States
- CA03927/CA/NCI NIH HHS/United States
- CA04326/CA/NCI NIH HHS/United States
- CA04457/CA/NCI NIH HHS/United States
- CA04919/CA/NCI NIH HHS/United States
- CA08025/CA/NCI NIH HHS/United States
- CA11028/CA/NCI NIH HHS/United States
- CA114558-02/CA/NCI NIH HHS/United States
- CA11789/CA/NCI NIH HHS/United States
- CA12449/CA/NCI NIH HHS/United States
- CA12644/CA/NCI NIH HHS/United States
- CA13612/CA/NCI NIH HHS/United States
- CA14028/CA/NCI NIH HHS/United States
- CA16385/CA/NCI NIH HHS/United States
- CA16450/CA/NCI NIH HHS/United States
- CA20319/CA/NCI NIH HHS/United States
- CA21115/CA/NCI NIH HHS/United States
- CA22433/CA/NCI NIH HHS/United States
- CA27057/CA/NCI NIH HHS/United States
- CA27525/CA/NCI NIH HHS/United States
- CA31946/CA/NCI NIH HHS/United States
- CA32102/CA/NCI NIH HHS/United States
- CA32291/CA/NCI NIH HHS/United States
- CA33601/CA/NCI NIH HHS/United States
- CA35090/CA/NCI NIH HHS/United States
- CA35091/CA/NCI NIH HHS/United States
- CA35113/CA/NCI NIH HHS/United States
- CA35119/CA/NCI NIH HHS/United States
- CA35176/CA/NCI NIH HHS/United States
- CA35192/CA/NCI NIH HHS/United States
- CA35261/CA/NCI NIH HHS/United States
- CA35262/CA/NCI NIH HHS/United States
- CA35281/CA/NCI NIH HHS/United States
- CA37981/CA/NCI NIH HHS/United States
- CA38926/CA/NCI NIH HHS/United States
- CA41287/CA/NCI NIH HHS/United States
- CA42777/CA/NCI NIH HHS/United States
- CA45377/CA/NCI NIH HHS/United States
- CA45450/CA/NCI NIH HHS/United States
- CA45560/CA/NCI NIH HHS/United States
- CA45807/CA/NCI NIH HHS/United States
- CA46113/CA/NCI NIH HHS/United States
- CA46282/CA/NCI NIH HHS/United States
- CA46368/CA/NCI NIH HHS/United States
- CA46441/CA/NCI NIH HHS/United States
- CA47559/CA/NCI NIH HHS/United States
- CA47577/CA/NCI NIH HHS/United States
- CA58348/CA/NCI NIH HHS/United States
- CA58416/CA/NCI NIH HHS/United States
- CA58666/CA/NCI NIH HHS/United States
- CA58861/CA/NCI NIH HHS/United States
- CA58882/CA/NCI NIH HHS/United States
- CA60138/CA/NCI NIH HHS/United States
- CA63844/CA/NCI NIH HHS/United States
- CA63845/CA/NCI NIH HHS/United States
- CA63850/CA/NCI NIH HHS/United States
- CA68183/CA/NCI NIH HHS/United States
- CA71323/CA/NCI NIH HHS/United States
- CA76447/CA/NCI NIH HHS/United States
- CA77440/CA/NCI NIH HHS/United States
- CA77651/CA/NCI NIH HHS/United States
- CA77658/CA/NCI NIH HHS/United States
- CA86780/CA/NCI NIH HHS/United States
- N01-CM-17003/CM/NCI NIH HHS/United States
- U01-CA70172-01/CA/NCI NIH HHS/United States
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical