title: Phase I/II study of combination therapy with S-1 and CPT-11 for metastatic colorectal cancer.
abstract: We conducted a Phase I/II study of combination therapy using CPT-11 and S-1 as a first-line treatment for metastatic colorectal cancer. The 28-day treatment cycle consisted of S-1 administered orally from day 1 to 21 and CPT-11 administered intravenously on days 1 and 15. In the Phase I portion, the dose of S-1 was fixed at 80 mg/m2/day, while CPT-11 was administered at a starting dose of 60 mg/m2 then stepped up in 20 mg/m2 increments. The maximum-tolerated dose was achieved at 80 mg/m2 of CPT-11, and the recommended dose was determined to be 60 mg/m2 of CPT-11. In the Phase II portion, this therapy exhibited a response rate of 58%, a median progression-free survival of 8.4 months, and a median overall survival of 18.7 months. Toxicity was generally mild and manageable. No patient showed grade 4 toxicity, and grade 3 toxicity was observed in only 18% of patients. The most frequently observed grade 3 toxicity was diarrhea, at a rate of 6%. The mean relative dose intensity of CPT-11 and S-1 was as high as 98 and 97%, respectively. In conclusion, combination therapy with CPT-11 and S-1 according to our treatment schedule is effective, safe and highly feasible for metastatic colorectal cancer patients. These data suggest that assessing this combination therapy in a Phase III study would be worthwhile.
authors.affiliation: Department of Surgery, Saga University Faculty of Medicine, Saga 849-8501, Japan. nakafusy@cc.saga-u.ac.jp.
authors.forename: Yuji
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authors.lastname: Nakafusa
authors.forename: Masayuki
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authors.lastname: Tanaka
authors.forename: Takao
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authors.lastname: Ohtsuka
authors.forename: Atsushi
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authors.lastname: Miyoshi
authors.forename: Naohiko
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authors.forename: Yoshihiko
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authors.lastname: Kitajima
authors.forename: Seiji
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authors.lastname: Sato
authors.forename: Sakiko
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authors.lastname: Mochinaga
authors.forename: Sawako
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authors.lastname: Dohi
authors.forename: Kohji
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authors.lastname: Miyazaki