Randomized phase II noncomparative trial of oral and intravenous doxifluridine plus levo-leucovorin in untreated patients with advanced colorectal carcinoma

Emilio Bajetta, Maria Di Bartolomeo, Luisa Somma, Monica Moreschi, Giuseppe Comella, Daniele Turci, Vittorio Gebbia, Alberto Scanni, Gianni Bordogna, Corrado Gallo Stampino

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BACKGROUND. Doxifluridine (5-dFUR) is a fluoropyrimidine derivative that has been shown to be active on a variety of solid tumors. The clinical use of intravenous (i.v.) 5-dFUR as a bolus injection or short term infusion has been limited because of its unpredictable severe neurotoxicity. Unlike fluorouracil (5-FU), 5-dFUR is effective when administered orally. METHODS. This randomized, parallel-group, Phase II trial of two schedules of 5-dFUR was conducted between April 1993 and September 1994. A total of 130 previously untreated patients with locally advanced or metastatic colorectal carcinoma were randomized to receive oral levo-leucovorin (l-leucovorin) 25 mg/dose followed by oral 5-dFUR 750 mg/m2 twice daily for 4 days every 12 days (arm A) or i.v. 1-leucovorin 25 mg/dose followed by i.v. 5-dFUR 3000 mg/m2 for 5 days every 21 days (arm B). RESULTS. The two treatment arms were well balanced in terms of age, sex, and disease extension. Metastases were present in more than 90% of the total population, with the liver being the most common site. A median of 7 oral courses (range, 1-15) and 9 intravenous courses (range, 1-9) were administered. Intent-to-treat analysis rate of the randomized patients revealed a response rate of 15% (95% confidence interval [CI], 7-26) in arm A and 41% (95% CI, 29-54) in arm B. However, 7 cases in arm A and 12 in arm B were inadequately treated, and the response rates, according to standard analysis, were respectively 17% (95% CI, 8-28) and 51% (95% CI, 37-65). The median time to treatment failure was 4 months (range, 1- 23) and 7 months (range, 1-9), respectively, for the two groups; median survival was 11 months (range, 1-24) in both groups. National Cancer Institute Grade 3 and 4 diarrhea were observed in 25% of the orally treated patients and in 18% of those receiving i.v. treatment. Stomatitis was reported mainly in aria B (15%). Mild and moderate neurotoxicity was observed in 6% of the patients in both arms; no severe neurotoxicity was reported. CONCLUSIONS: 5-dFUR with 1-leucovorin, administered either orally or intravenously, produces response rates that are similar to these offered by the regimens containing 5-FU that are usually used to treat advanced colorectal carcinoma. This study documents the good tolerance of the i.v. schedule administered as a 1-hour infusion; furthermore, oral administration seems to be promising and feasible as a home treatment.

Original languageEnglish
Pages (from-to)2087-2093
Number of pages7
Issue number10
Publication statusPublished - Nov 15 1996


  • chemotherapy
  • colorectal carcinoma
  • doxifluridine
  • fluoropyrimidine

ASJC Scopus subject areas

  • Cancer Research
  • Oncology


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