Background/Aims: To establish a safe and practical chemotherapeutic regimen using CPT-11 in combination with an oral 5FU derivative S-1 for patients with metastatic colorectal cancer, a phase I clinical trial was conducted in an outpatient setting. Methodology: Nine patients with metastatic colorectal cancer were enrolled. S-1 was administered at approved doses of 80mg/body/day to eligible patients with a body surface area (BSA) of less than 1.25m(2), 100mg/body/day to those with a BSA of 1.25-1.5m(2), and 120mg/body/day to those with a BSA of more than 1.5m(2), for 2 weeks followed by 1 week rest, comprising one treatment cycle of 3 weeks. CPT-11 was administered on day 8 of the S-1 cycle. The dose of CPT-11 was escalated from 60-120mg/m(2) by every 20mg/m(2) for every cohort consisting of at least 3 patients in order to define dose-limiting toxicity (DLT), maximal tolerated dose (MTD), and recommended dose (RD) in preparation for a phase II trial. Results: In regard to the hematologic toxicity, a decrease of WBC to less than grade 2 was observed in 2 patients until the dose was escalated to 100mg/m(2) of CPT-11, which delayed the treatment for 1 week in 1 patient. Regarding non-hematologic toxicity, fatigue and gastrointestinal toxicity, including anorexia and nausea/vomiting, at grades 1 and 2 were commonly observed throughout the dose levels. Diarrhea at grade 3 was observed at the 4th cycle of 100mg/m(2) CPT-11 in 2 of 3 patient both of whom required hospitalization. All patients were able to complete more than 3 treatment cycles, and 1 patient at 80mg/m(2) of CPT-11 was able to receive 31 treatment cycles. Observed tumor responses included 1 partial response (PR), 2 moderate responses, 4 stable diseases, and 2 progressive diseases. Serum CEA level decreased in 7 of the 9 patients enrolled. Conclusions: These results suggest that this treatment regimen using CPT-11 in combination with oral S-1 therapy is a safe regimen in an outpatient setting and effective for patients with metastatic colorectal cancer. The DLT is diarrhea at a MTD of 100mg/m(2) of CPT-11, and 80mg/m(2) CPT-11 is recommended for the next phase II trial.
