Background:Irinotecan (CPT-11) shows synergism withmitomycin-C (MMC) in a preclinical setting. The goals of this study wereto determine the maximum tolerated dose (MTD), the dose limitingtoxicity, the recommended dose (RD), and preliminary anti-tumor activityin a combined CPT-11 and MMC treatment of advanced gastric cancer.
Patients and methods:The study was designed to evaluateescalated doses of CPT-11 and MMC administered every two weeks. Fiveescalating dose levels were studied (CPT-11/MMC: 100/5; 125/5; 150/5;150/7; 150/10 mg/m2).
Results:Thirty-onepatients were enrolled. Thirty patients were assessable for toxicity andtumor response for 89 treatment cycles. The median age was 60 years(32–73 years), and most patients (90%) had a performancestatus of 0 to 1. Fourteen patients were previously treated and 17 werechemotherapy-naive. The MTD was CPT-11 150 mg/m2 plus MMC 10mg/m2, in which all three patients experienced grade 4neutropenia, including one episode of prolonged and one of febrileneutropenia, and one patient experienced grade 3 diarrhea during thefirst cycle. Fifteen partial responses were observed.
Conclusions:The RD based on this phase I–II study wasCPT-11 150 mg/m2 plus MMC 5 mg/m2 administeredevery two weeks. This combination demonstrates promising activityagainst advanced gastric cancer and warrants further investigation inanother phase II study.