Multicenter Phase III Study of Uracil/Tegafur and Oral Leucovorin Versus Fluorouracil and Leucovorin in Patients With Previously Untreated Metastatic Colorectal Cancer

Douillard, Jean-Yves; Hoff, Paulo M.; Skillings, Jamey; Eisenberg, Peter D.; Davidson, N.; Harper, Peter; Vincent, Mark; Lembersky, Barry C.; Thompson, Seth; Maniero, Antonella; Benner, Steven E.

doi:10.1200/jco.2002.04.123

Cited by 293 publications

(187 citation statements)

References 30 publications

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“…Benefits of these agents include convenience, elimination of risks from indwelling central venous catheters and a different toxic profile. They are of comparable efficacy to the Mayo regime but with less toxicity (Carmichael et al, 2002;Douillard et al, 2002;Twelves et al, 2005). Toxicity profiles of FOLFOX and FOLFIRI (Andre et al, 2004;O'Connell, 2004;Allegra and Sargent, 2005) may reduce the completion of these treatments, but fewer cycles of these regimes may be as efficacious as the completed Mayo regime.…”

Section: Discussionmentioning

confidence: 99%

Failure to complete adjuvant chemotherapy is associated with adverse survival in stage III colon cancer patients

et al. 2007

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Two recent North American studies have shown that completion of 5-fluorouracil (5FU)-based adjuvant chemotherapy is a major prognostic factor for the survival of elderly stage III colon cancer patients. The aim of the present study was to confirm this finding in a population-based series from Australia. The study cohort comprised 851 stage III colon cancer patients treated by surgery alone and 461 who initiated the Mayo chemotherapy regime. One-third of patients who initiated chemotherapy failed to complete more than three cycles of treatment. Independent predictors for failure to complete were treatment in district or rural hospitals, low socioeconomic index and treatment by a low-volume surgeon. Patients who failed to complete chemotherapy showed worse cancer-specific survival compared not only to those who completed treatment (HR ¼ 2.24; 95% confidence interval (CI) (1.66 -3.03), Po0.001) but also to those treated by surgery alone (HR ¼ 1.37; 95% CI (1.09 -1.72), P ¼ 0.008). The current and previous studies demonstrate the importance of completing adjuvant 5-FU-based chemotherapy for colon cancer. Further prospective studies are required to identify better the physiological and socioeconomic factors responsible for failure to complete chemotherapy so that appropriate improvements in health service delivery can be made.

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Section: Discussionmentioning

confidence: 99%

Failure to complete adjuvant chemotherapy is associated with adverse survival in stage III colon cancer patients

et al. 2007

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“…infusion of 5FU 250 mg m À2 (Ho et al, 1998). Two Phase III studies have been conducted to compare the efficacy and toxicity of modulation of UFT and LV with 5FU -LV (Carmichael et al, 2002;Douillard et al, 2002). Response rate and overall survival were similar, although a slight disadvantage in time to progression was observed for UFT -LV in one of the studies (3.8 vs 3.5 months; Po0.05) (Douillard et al, 2002).…”

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confidence: 99%

“…Two Phase III studies have been conducted to compare the efficacy and toxicity of modulation of UFT and LV with 5FU -LV (Carmichael et al, 2002;Douillard et al, 2002). Response rate and overall survival were similar, although a slight disadvantage in time to progression was observed for UFT -LV in one of the studies (3.8 vs 3.5 months; Po0.05) (Douillard et al, 2002). However, if we take these studies as a whole, it is acceptable to say that they are equivalent in efficacy and that UFT -LV has a more favourable toxicity profile, with less neutropenia, diarrhoea, nausea/vomiting and mucositis (Mayer, 2001).…”

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Phase II study of UFT and oxaliplatin in first-line treatment of advanced colorectal cancer

et al. 2004

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The purpose of this study was to evaluate the efficacy, assesed as response rate, and toxicity of UFT (Tegafur-Uracil) in combination with oxaliplatin as first-line treatment of advanced colorectal cancer (CRC). In all, 84 patients with recurrent or metastatic CRC with measurable disease were included. Treatment consisted of oxaliplatin 85 mg m À2 in 120-min intravenous (i.v.) infusion on days 1 and 15; i.v. l,leucovorin (l,LV) 250 mg m À2 given in 2 h on day 1, followed by oral UFT 390 mg m À2 on days 1 -14, and oral l,LV 7.5 mg/ 12 h on days 2 -14. Cycles were repeated every 28 days. A total of 492 cycles of chemotherapy were delivered with a median of six per patient (range 1 -12). There was one complete response (1%) and 28 partial responses (34%) for an overall response rate of 35% (95% confidence interval (CI): 24 -46%). A total of 36 patients (44%) had stable disease, whereas 17 (21%) had a progression. The median time to progression was 7.3 months and the median overall survival was 16.8 months. A prescheduled preliminary analysis was performed after inclusion of 16 patients who detected a high gastrointestinal toxicity, which led to a reduction of the UFT dose to 300 mg m À2 . With this new dosage, grade 3 -4 diarrhoea and grade 3 -4 nausea/vomiting dropped to 21 and 14% of patients, respectively. Other grade 3 -4 toxicities were stomatitis in one (1%), anaemia in three (5%), neutropenia in two (3%), thrombocytopenia in one(1%), fatigue in six (9%), peripheral sensory neuropathy in nine (14%) and laryngopharyngeal dysesthesia in two patients (2%). The combination of oxaliplatin and UFT -l,LV is an active, easy-to-administer regimen with moderate toxicity. Hence, this regimen is worthy of further investigation.

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“…The oral fluoropyrimidines UFT (tegafur:uracil in a 4 : 1 ratio) and capecitabine are more convenient and acceptable forms of chemotherapy than intravenous 5-FU and have been shown to have equivalent efficacy to intravenous bolus 5-FU plus LV in two randomised studies (Carmichael et al, 2002;Douillard et al, 2002). In addition, UFT appears to have a more favourable toxicity profile than bolus 5-FU-based regimens and UFT has also been shown to be more acceptable than intravenous 5-FU in terms of patient preference .…”

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confidence: 99%

Concurrent irinotecan, oxaliplatin and UFT in first-line treatment of metastatic colorectal cancer: a Phase I study

et al. 2007

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The feasibility of combining UFT plus leucovorin (LV) with alternating irinotecan and oxaliplatin was investigated in the first-line treatment of patients with advanced colorectal cancer. Twenty-five patients, median age 63 (range 24 -79) years, World Health Organisation performance status 0 -2 and median four marker lesions, received irinotecan 180 mg m À2 on day 1, oxaliplatin 85 -100 mg m À2 on day 15 and UFT 200 -300 mg m À2 day À1 with LV 90 mg day À1 , days 1 -21 of a 28-day cycle. Patients were treated in cohorts of three. At the highest dose (irinotecan 180 mg m À2 , oxaliplatin 100 mg m À2 and UFT 300 mg m À2 day À1 ), three of four patients experienced grade 3 toxicity. Diarrhoea, lethargy and vomiting were dose-limiting. Three of nine patients had grade 2 toxicities at the maximum tolerated dose (irinotecan 180 mg m À2 , oxaliplatin 100 mg m À2 and UFT 250 mg m À2 day À1 ). There were no grade 3 toxicities in the first month of therapy. The overall response rate was 71% in 21 evaluable patients; progression-free survival was 8.8 months. Alternating irinotecan and oxaliplatin plus UFT is an effective and well-tolerated first-line treatment for patients with advanced colorectal cancer. We recommend a dose of irinotecan 180 mg m À2 on day 1, oxaliplatin 100 mg m À2 on day 15 and UFT 250 mg m À2 day À1 with LV 90 mg day À1 on days 1 -21 of a 28-day cycle for future studies.

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Multicenter Phase III Study of Uracil/Tegafur and Oral Leucovorin Versus Fluorouracil and Leucovorin in Patients With Previously Untreated Metastatic Colorectal Cancer

Abstract: 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.

Cited by 293 publications

References 30 publications

Failure to complete adjuvant chemotherapy is associated with adverse survival in stage III colon cancer patients

Failure to complete adjuvant chemotherapy is associated with adverse survival in stage III colon cancer patients

Phase II study of UFT and oxaliplatin in first-line treatment of advanced colorectal cancer

Concurrent irinotecan, oxaliplatin and UFT in first-line treatment of metastatic colorectal cancer: a Phase I study

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