Back to Search
Start Over
A dose-escalating phase I of imatinib mesylate with fixed dose of metronomic cyclophosphamide in targeted olid tumours.
- Source :
- British Journal of Cancer; 11/12/2013, Vol. 109 Issue 10, p2574-2578, 5p
- Publication Year :
- 2013
-
Abstract
- Background:Preclinical findings suggest that imatinib mesylate (IM) and metronomic cyclophosphamide (MC) combination provides synergistic antiangiogenic activity on both pericytes and endothelial cells.Methods:We have designed a 3+3 dose-escalating phase I trial with a fixed dose of MC (50 mg two times daily) plus IM (400 mg per day; 300 and 400 mg two times daily). Enrolled patients had IM- and sutininib-refractory advanced gastrointestinal stromal tumours (GIST) (n=17), chordoma (n=7) and mucosal melanoma (n=2). Dose-limiting toxicities were monitored for the first 6 weeks. Progression-free survival (PFS) and response assessment are based on RECIST 1.0 guidelines. Pharmacokinetics of IM were measured before and after exposure to MC.Results:No dose-limiting toxicity was observed. Fourteen patients of the expanded cohort received 400 mg two times daily of IM with MC. Apart from a case of possibly related acute leukaemia occurring after 4 years of treatment, we did not see unexpected toxicity. No drug-drug pharmacokinetic interaction was observed. There was no objective response. We have observed long-lasting stable disease in chordoma patients (median PFS=10.2 months; range, 4.2-18+) and short-term stable disease in heavily GIST pretreated patients (median PFS=2.3 months; range, 2.1-6.6).Conclusion:This combination is feasible and may warrant further exploration in refractory GIST or chordoma patients. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00070920
- Volume :
- 109
- Issue :
- 10
- Database :
- Complementary Index
- Journal :
- British Journal of Cancer
- Publication Type :
- Academic Journal
- Accession number :
- 91932937
- Full Text :
- https://doi.org/10.1038/bjc.2013.648