Double modulation of 5-fluorouracil in the treatment of advanced colorectal carcinoma: Report of a trial with sequential methotrexate, intravenous (loading dose) folinic acid, 5-fluorouracil, and a literature review

Edward P. Balaban, Mateel Graham, Steve Perkins, Richard G. Sheehan, Eugene P. Frenkel, Michael Ross, Joan Bull, Brian Pruitt, Phillip Periman, Chris Ruud, James Luce

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4 Scopus citations


5-Fluorouracil (5-FU) modulation with either folinic acid (FA) or methotrexate (MTX) has improved 5-FU's potential cytoreductivity. We combined MTX and FA with 5-FU to further augment 5-FU's cytoreductivity. Patients (n = 34) with advanced colorectal carcinoma were first given intravenous MTX (escalated from 30 mg/m2 to 70 mg/m2). FA (100 mg/m2) was infused 17-24 hr later, followed by 5-FU (600 mg/m2). Oral rescue doses of FA were begun 24 hr after MTX. Patients were treated every 2 weeks. No previously treated patient (n = 6) responded. Eight of the remaining 28 (29% (95% confidence interval, 15-47% patients achieved a PR. Median survival was 9.3 months. Toxicity (primarily gastrointestinal) necessitated dosage modification in 10 patients (29% These results, in addition to a literature review, reveal that the manipulation of 5-FU by two modulating agents does not improve the response rate seen with single-agent modulation.

Original languageEnglish (US)
Pages (from-to)12-19
Number of pages8
JournalCancer Investigation
Issue number1
StatePublished - Jan 1 1994


ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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