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

Kuniaki Shirao, P. M. Hoff, A. Ohtsu, Patrick Loehrer, I. Hyodo, S. Wadler, R. G. Wadleigh, P. J. O'Dwyer, K. Muro, Y. Yamada, N. Boku, F. Nagashima, J. L. Abbruzzese

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)3466-3474
Number of pages9
JournalJournal of Clinical Oncology
Volume22
Issue number17
DOIs
StatePublished - 2004
Externally publishedYes

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Tegafur
Asian Americans
Uracil
Leucovorin
Colorectal Neoplasms
Japan
Pharmacokinetics
Joints
Diarrhea
Area Under Curve
Body Surface Area
Fluorouracil
Disease Progression

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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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. / Shirao, Kuniaki; Hoff, P. M.; Ohtsu, A.; Loehrer, Patrick; Hyodo, I.; Wadler, S.; Wadleigh, R. G.; O'Dwyer, P. J.; Muro, K.; Yamada, Y.; Boku, N.; Nagashima, F.; Abbruzzese, J. L.

In: Journal of Clinical Oncology, Vol. 22, No. 17, 2004, p. 3466-3474.

Research output: Contribution to journalArticle

Shirao, Kuniaki ; Hoff, P. M. ; Ohtsu, A. ; Loehrer, Patrick ; Hyodo, I. ; Wadler, S. ; Wadleigh, R. G. ; O'Dwyer, P. J. ; Muro, K. ; Yamada, Y. ; Boku, N. ; Nagashima, F. ; Abbruzzese, J. L. / 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. In: Journal of Clinical Oncology. 2004 ; Vol. 22, No. 17. pp. 3466-3474.
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abstract = "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.",
author = "Kuniaki Shirao and Hoff, {P. M.} and A. Ohtsu and Patrick Loehrer and I. Hyodo and S. Wadler and Wadleigh, {R. G.} and O'Dwyer, {P. J.} and K. Muro and Y. Yamada and N. Boku and F. Nagashima and Abbruzzese, {J. L.}",
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TY - JOUR

T1 - 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

T2 - Joint United States and Japan study of UFT/LV

AU - Shirao, Kuniaki

AU - Hoff, P. M.

AU - Ohtsu, A.

AU - Loehrer, Patrick

AU - Hyodo, I.

AU - Wadler, S.

AU - Wadleigh, R. G.

AU - O'Dwyer, P. J.

AU - Muro, K.

AU - Yamada, Y.

AU - Boku, N.

AU - Nagashima, F.

AU - Abbruzzese, J. L.

PY - 2004

Y1 - 2004

N2 - 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.

AB - 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.

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U2 - 10.1200/JCO.2004.05.017

DO - 10.1200/JCO.2004.05.017

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JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

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ER -