A phase II trial of gefitinib with 5-fluorouracil, leucovorin, and irinotecan in patients with colorectal cancer

摘要: Inhibition of epidermal growth factor receptor (EGFR) signalling contributes to the therapy colorectal cancer. Gefitinib, an oral EGFR tyrosine kinase inhibitor, shows supra-additive inhibition with irinotecan and fluoropyrimidines in xenograft models. We designed a study determine tolerability efficacy gefitinib combination irinotecan, infusional 5-fluorouracil (5-FU) leucovorin (LV), on 2-week schedule. Among 13 patients advanced cancer, 10 required dose reductions 5-FU because dehydration, diarrhoea, neutropenia, seven whom hospitalisation, three neutropenic fever. One patient achieved partial response had disease stabilisation. The this standard chemotherapy regimen is associated excessive toxicity, suggesting interaction at pharmacokinetic or pharmacodynamic level.