Overcoming resistance to chronomodulated 5-fluorouracil and folinic acid by the addition of chronomodulated oxaliplatin in advanced colorectal cancer patients

C. Garufi, S. Brienza, P. Pugliese, A. M. Aschelter, M. A. Bensmaine, F. Bertheault-Cvitkovic, C. Nisticò, S. Giunta, M. Caterino, D. Giannarelli, M. Cosimelli, F. Lévi, E. Terzoli

Research output: Contribution to journalArticlepeer-review

Abstract

The addition of oxaliplatin (L-OHP) to a 5-fluorouracil (5-FU)/leucovorin (FA) regimen was retrospectively evaluated in 35 consecutive advanced colorectal cancer patients after progression of disease. L-OHP, 25 mg/m2/day, was infused from 10.00-22.00 with a peak flow at 16.00 while 5-FU, 700 mg/m2/day and FA, 150 mg/m2/day of the l-form or 300 mg/m2/day of the racemic form, from 22.00 to 10.00 with a nocturnal peak at 4.00, for 5 days every 3 weeks in 24 patients and for 4 days every 2 weeks in the other 11. Diarrhea and sensitive neuropathy were the most relevant types of toxicity (17% of patients). An objective response was achieved in 8/35 patients (23%) [95% CL 9-37], stabilization in 15 patients (43%) which included five minor responses, and progression in 12. There was no relevant difference in quality of life assessed with the EORTC QLQ C30+3 questionnaire before and after treatment. Median duration of response and median progression-free survival were 6 months; median overall survival was 11 months. This retrospective study showed that it is possible to reverse resistance to chronomodulated 5-FU by adding chronomodulated L-OHP to the previous regimen; comparison with different schedules of this combination should be performed in order to identify the best tolerated and active regimen as second-line treatment of advanced colorectal cancer (C) 2000 Lippincott Williams and Wilkins.

Original languageEnglish
Pages (from-to)495-501
Number of pages7
JournalAnti-Cancer Drugs
Volume11
Issue number6
DOIs
Publication statusPublished - 2000

Keywords

  • 5-fluorouracil
  • Chronotherapy
  • Colorectal cancer
  • Folinic acid
  • Oxaliplatin

ASJC Scopus subject areas

  • Pharmacology
  • Cancer Research
  • Oncology

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