{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T11:45:22Z","timestamp":1790941522495,"version":"4.1.0"},"reference-count":51,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"17","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCO"],"published-print":{"date-parts":[[2002,9,1]]},"abstract":"<jats:p> PURPOSE: This phase III study was designed to demonstrate equivalence in survival of oral uracil\/tegafur (UFT) and oral leucovorin (LV) to conventional intravenous (IV) fluorouracil (5-FU) and LV in previously untreated metastatic colorectal carcinoma. Safety was also compared. <\/jats:p><jats:p> PATIENTS AND METHODS: Eight hundred sixteen patients were randomized to receive either UFT (300 mg\/m<jats:sup>2<\/jats:sup>\/d) and LV (75 or 90 mg\/d) for 28 days every 35 days or IV bolus 5-FU (425 mg\/m<jats:sup>2<\/jats:sup>\/d) and LV (20 mg\/m<jats:sup>2<\/jats:sup>\/d) for 5 days every 28 days. <\/jats:p><jats:p> RESULTS: UFT\/LV produced survival comparable to the IV 5-FU\/LV regimen. Median survival was 12.4 months (95% confidence interval [CI], 11.2 to 13.6 months) with UFT\/LV and 13.4 months (95% CI, 11.6 to 15.4 months) with 5-FU\/LV (P = .630). The hazard ratio for survival was 0.964 (95.6% CI, 0.826 to 1.125), supporting equivalent survival. The overall response rate did not differ between treatment arms (UFT\/LV, 11.7%; 5-FU\/LV, 14.5%; P = .232). Median time to progression favored 5-FU\/LV (UFT\/LV, 3.5 months; 5-FU\/LV, 3.8 months; P = .011), but tumor assessment schedules differed between arms. UFT\/LV significantly improved safety compared with 5-FU\/LV. Diarrhea, nausea and vomiting, and stomatitis and mucositis were significantly less frequent with UFT\/LV, as was myelosuppression. Patients treated with UFT\/LV had fewer episodes of febrile neutropenia (P &lt; .001) and documented infections (P &lt; .05). Increased bilirubin, without other liver function abnormalities, was observed more often with UFT\/LV (P &lt; .001). Concomitant medications were more frequent with 5-FU\/LV, including use of antibiotics, growth factors, and antiemetics. <\/jats:p><jats:p> CONCLUSION: UFT\/LV provided a safer, more convenient oral alternative to a standard bolus IV 5-FU\/LV regimen for metastatic colorectal cancer while producing equivalent survival. <\/jats:p>","DOI":"10.1200\/jco.2002.04.123","type":"journal-article","created":{"date-parts":[[2002,8,29]],"date-time":"2002-08-29T19:45:09Z","timestamp":1030650309000},"page":"3605-3616","source":"Crossref","is-referenced-by-count":256,"title":["Multicenter Phase III Study of Uracil\/Tegafur and Oral Leucovorin Versus Fluorouracil and Leucovorin in Patients With Previously Untreated Metastatic Colorectal Cancer"],"prefix":"10.1200","volume":"20","author":[{"given":"Jean-Yves","family":"Douillard","sequence":"first","affiliation":[{"name":"From the Centre Ren\u00e9 Gauducheau, Nantes, France; University of Texas, M.D. Anderson Cancer Center, Houston, TX; Nova Scotia Cancer Center, Halifax, Canada; California Healthcare, Greenbrae, CA; North Middlesex and Guy\u2019s Hospital, London, United Kingdom; London Regional Cancer Center, London, Canada; University of Pittsburgh Cancer Center, Pittsburgh, PA; and Bristol-Myers Squibb Company, Wallingford, CT."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulo M.","family":"Hoff","sequence":"additional","affiliation":[{"name":"From the Centre Ren\u00e9 Gauducheau, Nantes, France; University of Texas, M.D. Anderson Cancer Center, Houston, TX; Nova Scotia Cancer Center, Halifax, Canada; California Healthcare, Greenbrae, CA; North Middlesex and Guy\u2019s Hospital, London, United Kingdom; London Regional Cancer Center, London, Canada; University of Pittsburgh Cancer Center, Pittsburgh, PA; and Bristol-Myers Squibb Company, Wallingford, CT."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamey R.","family":"Skillings","sequence":"additional","affiliation":[{"name":"From the Centre Ren\u00e9 Gauducheau, Nantes, France; University of Texas, M.D. Anderson Cancer Center, Houston, TX; Nova Scotia Cancer Center, Halifax, Canada; California Healthcare, Greenbrae, CA; North Middlesex and Guy\u2019s Hospital, London, United Kingdom; London Regional Cancer Center, London, Canada; University of Pittsburgh Cancer Center, Pittsburgh, PA; and Bristol-Myers Squibb Company, Wallingford, CT."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Eisenberg","sequence":"additional","affiliation":[{"name":"From the Centre Ren\u00e9 Gauducheau, Nantes, France; University of Texas, M.D. Anderson Cancer Center, Houston, TX; Nova Scotia Cancer Center, Halifax, Canada; California Healthcare, Greenbrae, CA; North Middlesex and Guy\u2019s Hospital, London, United Kingdom; London Regional Cancer Center, London, Canada; University of Pittsburgh Cancer Center, Pittsburgh, PA; and Bristol-Myers Squibb Company, Wallingford, CT."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neville","family":"Davidson","sequence":"additional","affiliation":[{"name":"From the Centre Ren\u00e9 Gauducheau, Nantes, France; University of Texas, M.D. Anderson Cancer Center, Houston, TX; Nova Scotia Cancer Center, Halifax, Canada; California Healthcare, Greenbrae, CA; North Middlesex and Guy\u2019s Hospital, London, United Kingdom; London Regional Cancer Center, London, Canada; University of Pittsburgh Cancer Center, Pittsburgh, PA; and Bristol-Myers Squibb Company, Wallingford, CT."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Harper","sequence":"additional","affiliation":[{"name":"From the Centre Ren\u00e9 Gauducheau, Nantes, France; University of Texas, M.D. Anderson Cancer Center, Houston, TX; Nova Scotia Cancer Center, Halifax, Canada; California Healthcare, Greenbrae, CA; North Middlesex and Guy\u2019s Hospital, London, United Kingdom; London Regional Cancer Center, London, Canada; University of Pittsburgh Cancer Center, Pittsburgh, PA; and Bristol-Myers Squibb Company, Wallingford, CT."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark D.","family":"Vincent","sequence":"additional","affiliation":[{"name":"From the Centre Ren\u00e9 Gauducheau, Nantes, France; University of Texas, M.D. Anderson Cancer Center, Houston, TX; Nova Scotia Cancer Center, Halifax, Canada; California Healthcare, Greenbrae, CA; North Middlesex and Guy\u2019s Hospital, London, United Kingdom; London Regional Cancer Center, London, Canada; University of Pittsburgh Cancer Center, Pittsburgh, PA; and Bristol-Myers Squibb Company, Wallingford, CT."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barry C.","family":"Lembersky","sequence":"additional","affiliation":[{"name":"From the Centre Ren\u00e9 Gauducheau, Nantes, France; University of Texas, M.D. Anderson Cancer Center, Houston, TX; Nova Scotia Cancer Center, Halifax, Canada; California Healthcare, Greenbrae, CA; North Middlesex and Guy\u2019s Hospital, London, United Kingdom; London Regional Cancer Center, London, Canada; University of Pittsburgh Cancer Center, Pittsburgh, PA; and Bristol-Myers Squibb Company, Wallingford, CT."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seth","family":"Thompson","sequence":"additional","affiliation":[{"name":"From the Centre Ren\u00e9 Gauducheau, Nantes, France; University of Texas, M.D. Anderson Cancer Center, Houston, TX; Nova Scotia Cancer Center, Halifax, Canada; California Healthcare, Greenbrae, CA; North Middlesex and Guy\u2019s Hospital, London, United Kingdom; London Regional Cancer Center, London, Canada; University of Pittsburgh Cancer Center, Pittsburgh, PA; and Bristol-Myers Squibb Company, Wallingford, CT."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Maniero","sequence":"additional","affiliation":[{"name":"From the Centre Ren\u00e9 Gauducheau, Nantes, France; University of Texas, M.D. Anderson Cancer Center, Houston, TX; Nova Scotia Cancer Center, Halifax, Canada; California Healthcare, Greenbrae, CA; North Middlesex and Guy\u2019s Hospital, London, United Kingdom; London Regional Cancer Center, London, Canada; University of Pittsburgh Cancer Center, Pittsburgh, PA; and Bristol-Myers Squibb Company, Wallingford, CT."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven E.","family":"Benner","sequence":"additional","affiliation":[{"name":"From the Centre Ren\u00e9 Gauducheau, Nantes, France; 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