Phase I-II study of irinotecan combined with mitomycin-C in patients with advanced gastric cancer

Background: Irinotecan (CPT-11) shows synergism with mitomycin-C (MMC) in a preclinical setting. The goals of this study were to determine the maximum tolerated dose (MTD), the dose limiting toxicity, the recommended dose (RD), and preliminary anti-tumor activity in a combined CPT-11 and MMC treatment of advanced gastric cancer. Patients and methods: The study was designed to evaluate escalated doses of CPT-11 and MMC administered every two weeks. Five escalating dose levels were studied (CPT-11/MMC: 100/5; 125/5; 150/5; 150/7; 150/10 mg/m(2)). Results: Thirty-one patients were enrolled. Thirty patients were assessable for toxicity and tumor response for 89 treatment cycles. The median age was 60 years (32-73 years), and most patients (90%) had a performance status of 0 to 1. Fourteen patients were previously treated and 17 were chemotherapy-naive. The MTD was CPT-11 150 mg/m(2) plus MMC 10 mg/m(2), in which all three patients experienced grade 4 neutropenia, including one episode of prolonged and one of febrile neutropenia, and one patient experienced grade 3 diarrhea during the first cycle. Fifteen partial responses were observed. Conclusions: The RD based on this phase I-II study was CPT-11 150 mg/m(2) plus MMC 5 mg/m(2) administered every two weeks. This combination demonstrates promising activity against advanced gastric cancer and warrants further investigation in another phase II study.