Purpose The GONO-FOLFOXIRI regimen demonstrated higher activity and eYcacy than FOLFIRI in metastatic colorectal cancer patients. The aim of this study was to determine the maximum tolerated dose of capecitabine, in substitution of 5-fluorouracil, combined with oxaliplatin and irinotecan and to evaluate the pharmacokinetics of the drugs. Patients and methods. We treated 15 patients with escalating doses of capecitabine (from day 1 to 7) and Wxed doses of oxaliplatin (85 mg/m2) plus irinotecan (165 mg/m2 (both administered on day 1), repeated every 2 weeks. Pharmacokinetic analysis was performed on plasma samples collected at the Wrst cycle of treatment. Results. The maximum tolerated dose of capecitabine resulted 2,000 mg/m2/day, with diarrhea being the only dose-limiting toxicity. Large interpatient variability in the pharmacokinetic parameters of investigated drugs was observed. Results in terms of activity are promising. Conclusions. At the maximum tolerated dose of capecitabine of 2,000 mg/m2/day the combination is feasible with promising activity and deserves further investigations.

A dose finding and pharmacokinetic study of capecitabine in combination with oxaliplatin and irinotecan in metastatic colorectal cancer

MASI G;DI PAOLO, ANTONELLO;BOCCI, GUIDO;FALCONE, ALFREDO
2009-01-01

Abstract

Purpose The GONO-FOLFOXIRI regimen demonstrated higher activity and eYcacy than FOLFIRI in metastatic colorectal cancer patients. The aim of this study was to determine the maximum tolerated dose of capecitabine, in substitution of 5-fluorouracil, combined with oxaliplatin and irinotecan and to evaluate the pharmacokinetics of the drugs. Patients and methods. We treated 15 patients with escalating doses of capecitabine (from day 1 to 7) and Wxed doses of oxaliplatin (85 mg/m2) plus irinotecan (165 mg/m2 (both administered on day 1), repeated every 2 weeks. Pharmacokinetic analysis was performed on plasma samples collected at the Wrst cycle of treatment. Results. The maximum tolerated dose of capecitabine resulted 2,000 mg/m2/day, with diarrhea being the only dose-limiting toxicity. Large interpatient variability in the pharmacokinetic parameters of investigated drugs was observed. Results in terms of activity are promising. Conclusions. At the maximum tolerated dose of capecitabine of 2,000 mg/m2/day the combination is feasible with promising activity and deserves further investigations.
2009
Fornaro, L; Masi, G; Bursi, S; Loupakis, F; Vasile, E; Antonuzzo, A; Chiara, S; Pfanner, E; DI PAOLO, Antonello; Bocci, Guido; DEL TACCA, M; Falcone, ...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11568/196423
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