10 research outputs found
A phase I clinical and pharmacokinetic study of capecitabine (XelodaÂź) and irinotecan combination therapy (XELIRI) in patients with metastatic gastrointestinal tumours
Capecitabine is a highly active oral fluoropyrimidine that is an attractive alternative to 5-fluorouracil in colorectal cancer treatment. The current study, undertaken in 27 patients with gastrointestinal tumours, aimed to assess the toxicity and potential for significant pharmacokinetic interactions of a combination regimen incorporating capecitabine with 3-weekly irinotecan (XELIRI). Irinotecan (200 and 250âmgâmâ2) was administered as a 90-min infusion on day 1 in combination with escalating capecitabine doses (700â1250âmgâmâ2 twice daily) administered on days 2â15 of a 3-week treatment cycle. Pharmacokinetics were characterised on days 1 and 2 of the first two cycles. A total of 103 treatment cycles were administered. The principal dose-limiting toxicities were diarrhoea and neutropenia. Capecitabine 1150âmgâmâ2 twice daily with irinotecan 250âmgâmâ2 was identified as the maximum-tolerated dose and capecitabine 1000âmgâmâ2 with irinotecan 250âmgâmâ2 was identified as the recommended dose for further study. Analyses confirmed that there were no significant pharmacokinetic interactions between the two agents. The combination was clinically active, with complete and partial responses achieved in heavily pretreated patients. This study indicates that XELIRI is a potentially feasible and clinically active regimen in patients with advanced gastrointestinal cancer