Back to Search
Start Over
Imatinib plus low-dose doxorubicin in patients with advanced gastrointestinal stromal tumors refractory to high-dose imatinib: a phase I-II study by the Spanish Group for Research on Sarcomas.
- Source :
-
Cancer (0008543X) . 8/1/2010, Vol. 116 Issue 15, p3692-3701. 10p. - Publication Year :
- 2010
-
Abstract
- <bold>Background: </bold>In KIT-expressing Ewing sarcoma cell lines, the addition of doxorubicin to imatinib increases apoptosis, compared with imatinib or doxorubicin alone. On the basis of these in vitro data, the authors conducted a phase 1-2 trial of doxorubicin with imatinib in patients with gastrointestinal sarcoma tumors refractory to high-dose imatinib therapy. <bold>Methods: </bold>Patients with metastatic gastrointestinal sarcoma tumor resistant to imatinib at 400 mg by mouth (p.o.) twice a day were eligible for this multicenter study, and received imatinib (400 mg p.o. every day [q.d.]) concomitantly with doxorubicin 15-20 mg/m2/weekly for 4 cycles (monthly cycles), followed by imatinib (400 mg p.o. q.d.) maintenance in nonprogressive patients. Spiral computed tomography and positron emission tomography with F18-fluorodeoxyglucose were done basally and after 2 months of therapy to evaluate response. An in vitro study assessed the effect of combining imatinib and doxorubicin. <bold>Results: </bold>Twenty-six patients with progressive gastrointestinal sarcoma tumor were entered in the study. Treatment was well tolerated. Three (14%) of 22 evaluable patients had partial responses per Response Evaluation Criteria in Solid Tumors, and 8 (36%) had clinical benefit (partial response or stable disease for >or=6 months). Median progression-free survival (PFS) was 100 days (95% confidence interval [CI], 62-138), and median survival was 390 days (95% CI, 264-516). Interestingly, PFS was 211 days (95% CI, 52-370) in patients with wild type (WT) KIT and 82 days (95% CI, 53-111) in non-WT patients (10 mutant, 6 not assessed). A synergistic effect on cell line proliferation and apoptosis was found with imatinib and doxorubicin combination. <bold>Conclusions: </bold>Low-dose chemobiotherapy combination showed promising activity in heavily pretreated gastrointestinal sarcoma tumor patients, especially in those with WT-KIT genotype. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 0008543X
- Volume :
- 116
- Issue :
- 15
- Database :
- Academic Search Index
- Journal :
- Cancer (0008543X)
- Publication Type :
- Academic Journal
- Accession number :
- 105065637
- Full Text :
- https://doi.org/10.1002/cncr.25111