Phase II trial of uracil and tegafur plus oral leucovorin

An effective oral regimen in the treatment of metastatic colorectal carcinoma

Richard Pazdur, Yvonne Lassere, Virginia Rhodes, Jaffer A. Ajani, Steven M. Sugarman, Yehuda Z. Patt, Dennie V. Jones, Avi Markowitz, James L. Abbruzzese, Beth Bready, Bernard Levin

    Research output: Contribution to journalArticle

    220 Citations (Scopus)

    Abstract

    Purpose: To determine the activity and evaluate the toxicity of uracil and tegafur in a 4:1 molar concentration (UFT; Taiho Pharmaceutical Ltd, Tokyo, Japan) plus oral calcium leucovorin in the treatment of patients with advanced colorectal carcinoma. Patients and Methods: Forty-five patients with advanced, bidimensionally measurable metastatic colorectal carcinoma were enrolled onto the trial. None of the patients had received prior chemotherapy or biologic therapy for advanced disease. Patients received either 350 or 300 mg/m2/d UFT plus 150 mg/d leucovorin administered orally in divided daily doses every 8 hours for 28 days followed by a 7-day rest period. Response was evaluated after two courses of therapy. Results: Eighteen patients (three treated at 350 mg/m2/d and 15 at 300 mg/m2/d) had partial responses, and one patient had a complete response (response rate, 42.2%; 95% confidence interval, 28% to 58%). Responses were observed in sites that included liver (n = 18), lung (n = 6), and bone (n = 1). Of seven patients who received 350 mg/m2 UFT, prolonged grade 3 diarrhea developed in five; this resulted in a reduction in the UFT starting dose to 300 mg/m2/d in the remaining 38 patients. Grade 1 or 2 toxic effects included diarrhea, nausea, vomiting, abdominal cramping, anorexia, fatigue, oral mucositis, excessive lacrimation, and rash. Among 38 patients who received the 300-mg/m2/d dose, grade 3 toxic reactions included diarrhea (n = 4), vomiting (n = 2), abdominal cramping (n = 1), and fatigue (n = 2). Conclusion: UFT 300 mg/m2/d plus oral leucovorin 150 mg/d administered for 28 days demonstrated significant activity against metastatic colorectal carcinoma. This oral regimen was well tolerated and devoid of the neutropenia or significant oral mucositis that complicates intravenous schedules of fluorouracil (5-FU) plus leucovorin. The results of this clinical trial will serve as the basis for a randomized phase III study to compare this oral schedule of UFT plus leucovorin with intravenous 5-FU plus leucovorin to determine the relative efficacy, impact on quality of life, and cost of the two regimens.

    Original languageEnglish (US)
    Pages (from-to)2296-2300
    Number of pages5
    JournalJournal of Clinical Oncology
    Volume12
    Issue number11
    StatePublished - Nov 1994

    Fingerprint

    Tegafur
    Uracil
    Leucovorin
    Colorectal Neoplasms
    Fluorouracil
    Therapeutics
    Diarrhea
    Stomatitis
    Poisons
    Vomiting
    Fatigue
    Appointments and Schedules
    Biological Therapy
    Tokyo
    Anorexia
    Exanthema
    Neutropenia
    Nausea
    Japan
    Quality of Life

    ASJC Scopus subject areas

    • Cancer Research
    • Oncology

    Cite this

    Pazdur, R., Lassere, Y., Rhodes, V., Ajani, J. A., Sugarman, S. M., Patt, Y. Z., ... Levin, B. (1994). Phase II trial of uracil and tegafur plus oral leucovorin: An effective oral regimen in the treatment of metastatic colorectal carcinoma. Journal of Clinical Oncology, 12(11), 2296-2300.

    Phase II trial of uracil and tegafur plus oral leucovorin : An effective oral regimen in the treatment of metastatic colorectal carcinoma. / Pazdur, Richard; Lassere, Yvonne; Rhodes, Virginia; Ajani, Jaffer A.; Sugarman, Steven M.; Patt, Yehuda Z.; Jones, Dennie V.; Markowitz, Avi; Abbruzzese, James L.; Bready, Beth; Levin, Bernard.

    In: Journal of Clinical Oncology, Vol. 12, No. 11, 11.1994, p. 2296-2300.

    Research output: Contribution to journalArticle

    Pazdur, R, Lassere, Y, Rhodes, V, Ajani, JA, Sugarman, SM, Patt, YZ, Jones, DV, Markowitz, A, Abbruzzese, JL, Bready, B & Levin, B 1994, 'Phase II trial of uracil and tegafur plus oral leucovorin: An effective oral regimen in the treatment of metastatic colorectal carcinoma', Journal of Clinical Oncology, vol. 12, no. 11, pp. 2296-2300.
    Pazdur, Richard ; Lassere, Yvonne ; Rhodes, Virginia ; Ajani, Jaffer A. ; Sugarman, Steven M. ; Patt, Yehuda Z. ; Jones, Dennie V. ; Markowitz, Avi ; Abbruzzese, James L. ; Bready, Beth ; Levin, Bernard. / Phase II trial of uracil and tegafur plus oral leucovorin : An effective oral regimen in the treatment of metastatic colorectal carcinoma. In: Journal of Clinical Oncology. 1994 ; Vol. 12, No. 11. pp. 2296-2300.
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    abstract = "Purpose: To determine the activity and evaluate the toxicity of uracil and tegafur in a 4:1 molar concentration (UFT; Taiho Pharmaceutical Ltd, Tokyo, Japan) plus oral calcium leucovorin in the treatment of patients with advanced colorectal carcinoma. Patients and Methods: Forty-five patients with advanced, bidimensionally measurable metastatic colorectal carcinoma were enrolled onto the trial. None of the patients had received prior chemotherapy or biologic therapy for advanced disease. Patients received either 350 or 300 mg/m2/d UFT plus 150 mg/d leucovorin administered orally in divided daily doses every 8 hours for 28 days followed by a 7-day rest period. Response was evaluated after two courses of therapy. Results: Eighteen patients (three treated at 350 mg/m2/d and 15 at 300 mg/m2/d) had partial responses, and one patient had a complete response (response rate, 42.2{\%}; 95{\%} confidence interval, 28{\%} to 58{\%}). Responses were observed in sites that included liver (n = 18), lung (n = 6), and bone (n = 1). Of seven patients who received 350 mg/m2 UFT, prolonged grade 3 diarrhea developed in five; this resulted in a reduction in the UFT starting dose to 300 mg/m2/d in the remaining 38 patients. Grade 1 or 2 toxic effects included diarrhea, nausea, vomiting, abdominal cramping, anorexia, fatigue, oral mucositis, excessive lacrimation, and rash. Among 38 patients who received the 300-mg/m2/d dose, grade 3 toxic reactions included diarrhea (n = 4), vomiting (n = 2), abdominal cramping (n = 1), and fatigue (n = 2). Conclusion: UFT 300 mg/m2/d plus oral leucovorin 150 mg/d administered for 28 days demonstrated significant activity against metastatic colorectal carcinoma. This oral regimen was well tolerated and devoid of the neutropenia or significant oral mucositis that complicates intravenous schedules of fluorouracil (5-FU) plus leucovorin. The results of this clinical trial will serve as the basis for a randomized phase III study to compare this oral schedule of UFT plus leucovorin with intravenous 5-FU plus leucovorin to determine the relative efficacy, impact on quality of life, and cost of the two regimens.",
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    T2 - An effective oral regimen in the treatment of metastatic colorectal carcinoma

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    AU - Lassere, Yvonne

    AU - Rhodes, Virginia

    AU - Ajani, Jaffer A.

    AU - Sugarman, Steven M.

    AU - Patt, Yehuda Z.

    AU - Jones, Dennie V.

    AU - Markowitz, Avi

    AU - Abbruzzese, James L.

    AU - Bready, Beth

    AU - Levin, Bernard

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    N2 - Purpose: To determine the activity and evaluate the toxicity of uracil and tegafur in a 4:1 molar concentration (UFT; Taiho Pharmaceutical Ltd, Tokyo, Japan) plus oral calcium leucovorin in the treatment of patients with advanced colorectal carcinoma. Patients and Methods: Forty-five patients with advanced, bidimensionally measurable metastatic colorectal carcinoma were enrolled onto the trial. None of the patients had received prior chemotherapy or biologic therapy for advanced disease. Patients received either 350 or 300 mg/m2/d UFT plus 150 mg/d leucovorin administered orally in divided daily doses every 8 hours for 28 days followed by a 7-day rest period. Response was evaluated after two courses of therapy. Results: Eighteen patients (three treated at 350 mg/m2/d and 15 at 300 mg/m2/d) had partial responses, and one patient had a complete response (response rate, 42.2%; 95% confidence interval, 28% to 58%). Responses were observed in sites that included liver (n = 18), lung (n = 6), and bone (n = 1). Of seven patients who received 350 mg/m2 UFT, prolonged grade 3 diarrhea developed in five; this resulted in a reduction in the UFT starting dose to 300 mg/m2/d in the remaining 38 patients. Grade 1 or 2 toxic effects included diarrhea, nausea, vomiting, abdominal cramping, anorexia, fatigue, oral mucositis, excessive lacrimation, and rash. Among 38 patients who received the 300-mg/m2/d dose, grade 3 toxic reactions included diarrhea (n = 4), vomiting (n = 2), abdominal cramping (n = 1), and fatigue (n = 2). Conclusion: UFT 300 mg/m2/d plus oral leucovorin 150 mg/d administered for 28 days demonstrated significant activity against metastatic colorectal carcinoma. This oral regimen was well tolerated and devoid of the neutropenia or significant oral mucositis that complicates intravenous schedules of fluorouracil (5-FU) plus leucovorin. The results of this clinical trial will serve as the basis for a randomized phase III study to compare this oral schedule of UFT plus leucovorin with intravenous 5-FU plus leucovorin to determine the relative efficacy, impact on quality of life, and cost of the two regimens.

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