A phase I trial of 5-day chronomodulated infusion of 5-fluorouracil and 1-folinic acid in patients with metastatic colorectal cancer

C. Garufi, F. Lévi, A. M. Aschelter, R. Pace, S. Giunta, C. Nisticò, D. A P Gallà, G. F. Silecchia, F. Franchi, C. Narduzzi, E. Terzoli

Research output: Contribution to journalArticlepeer-review

Abstract

The aim of this phase I study was to establish the maximum tolerated dose (MTD) of 5-fluorouracil (5-FU), administered as a 5-day chronomodulated infusion in combination with 1-folinic acid (FA) to ambulatory metastatic colorectal cancer patients. Consecutive cohorts of 6 patients were given 5- FU and FA infusions from 10.00 p.m. to 10.00 a.m. with peak delivery at 4.00 a.m. by means of a multichannel programmable pump. The FA dose was always the same (150 mg/m2/d). For the first cohort, the 5-FU dose level was 600 mg/m2/d at the first course, escalated by 100 mg/m2 for each subsequent cohort. Intrapatient dose was also escalated by 100 mg/m2 if toxicity was less than grade 2. The courses were repeated every 3 weeks. Thirty-four patients (17 previously treated) received a total of 154 courses. Dose- limiting toxicity consisted of stomatitis and diarrhoea. No significant haematological, cutaneous or cardiac toxicity was encountered. The MTD of 5- FU was reached at the fourth level (first course at 900 mg/m2/d equal to 4500 mg/m2/course) with 5-FU increased to 1100 mg/m2/d (5500 mg/m2/course) in 4 patients. The received 5-FU dose intensity (DI) over the first 3 courses at this level was 1318 mg/m2/week. Thirty-three patients were assessed for response. An objective response was achieved in 1 out of the 13 previously- treated and in 8 out of the 20 previously-untreated patients. The chronomodulated infusion of 5-FU at a dose of 900 mg/m2/d, together with FA at 150 mg/m2/d for 5 days, was safely delivered to outpatients with metastatic colorectal cancer. The low toxic profile and activity of this regimen in previously untreated patients deserves further exploration for the treatment of 5-FU-sensitive tumours.

Original languageEnglish
Pages (from-to)1566-1571
Number of pages6
JournalEuropean Journal of Cancer
Volume33
Issue number10
DOIs
Publication statusPublished - Sep 1997

Keywords

  • 5-fluorouracil
  • Chronotherapy
  • Colorectal cancer

ASJC Scopus subject areas

  • Cancer Research
  • Hematology
  • Oncology

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