Originally published as JCO Early Release 10.1200/JCO.2004.05.017 on July 26 2004

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Comparison of the Efficacy, Toxicity, and Pharmacokinetics of a Uracil/Tegafur (UFT) Plus Oral Leucovorin (LV) Regimen Between Japanese and American Patients With Advanced Colorectal Cancer: Joint United States and Japan Study of UFT/LV

From the Division of Gastrointestinal Oncology, National Cancer Center Hospital, Tokyo; Division of Gastrointestinal Oncology/Digestive Endoscopy, National Cancer Center Hospital East, Chiba; Department of Internal Medicine, National Shikoku Cancer Center, Ehime, Japan; Division of Hematology & Medical Oncology, Department of Medicine, Weill Medical College of Cornell University, Ithaca, NY; Oncology Section, Department of Veterans Affairs Medical Center, Washington, DC; Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA; Department of Gastrointestinal Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX; Section of Hematology & Oncology, Indiana University Cancer Center and The Walther Cancer Institute, Indianapolis, IN

Address reprint requests to Kuniaki Shirao, MD, Division of Gastrointestinal Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan; e-mail: kshirao{at}gan2.ncc.go.jp

PURPOSE: To compare the efficacy, toxicities, and pharmacokinetics of an oral regimen consisting of uracil/tegafur (UFT) and leucovorin (LV) between Japanese patients and patients in the United States with previously untreated metastatic colorectal cancer.

PATIENTS AND METHODS: Forty-four Japanese patients and 45 patients in the United States were enrolled in concurrent nonrandomized phase II trials. UFT 300 mg/m²/d and leucovorin 75 mg/d were administered orally for 28 days followed by a 7-day rest period. The total daily dose of each drug was divided into three equal doses. Treatment was repeated every 5 weeks until disease progression. Blood samples for the pharmacokinetic study were obtained after the initial dose on day 1 of the first course.

RESULTS: The response rate for the Japanese patients and the patients in the United States was 36.4% (95% CI, 22.4% to 52.2%) and 34.1% (95% CI, 20.5% to 49.9%), respectively. The only major toxicity was diarrhea, and other toxicities were mild in both populations. The incidence of grade 3 or higher diarrhea in the Japanese and Americans was 9% and 22%, respectively. Although the area under the curve and maximum concentration of fluorouracil were found to be slightly higher in the Japanese patients than the patients in the United States, and area under the curve–adjusted body surface area appeared to be comparable between the two groups.

CONCLUSION: The efficacy and pharmacokinetic parameters of UFT and LV are comparable in Japanese and American patients; however, a difference in toxicity profile, specifically diarrhea, was noted. This oral regimen of UFT and LV is considered to have similar activity against metastatic colorectal cancer and to have acceptable toxicity in patients in both countries.

Supported by the Taiho Pharmaceutical Company, Tokyo, Japan.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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