Phase I/II study of sequential therapy with irinotecan and S-1 for metastatic colorectal cancer

Background: Both irinotecan (CPT-11) and S-1 are active against colorectal cancer; however, as S-1 is a prodrug of 5-fluorouracil (5-FU), 5-FU and its metabolites might inhibit the antitumour effect of CPT-11. Therefore, we designed a sequential combination, in which CPT-11 infusion was given on day 1 and S-1 was given orally at 80 mg m 2 per day on days 3-16 every 3 weeks.Methods: Twelve patients entered the phase I study, and the recommended doses were determined as a CPT-11 dose of 150 mg m 2 and an S-1 dose of 80 mg m 2.Results:In all, 36 patients entered the phase II study, of whom 4 and 16 had complete and partial responses. The overall response rate was 55.6% (95% confidence interval, 38.1-72.1%), and median progression-free survival was 7.7 months (95% confidence interval, 4.8-12.6 months). Grade 3 neutropenia was the most common haematological toxicity and occurred in 6.5% of 215 treatment courses. Grade 3 non-haematological toxicities included anorexia (1.4%) and diarrhoea (0.9%). There was no grade 4 toxicity of any kind. Conclusion: Our results suggest that this regimen is convenient, safe and promising, compared with conventional regimens for patients with metastatic colorectal cancer.