5-Fluorouracil administered as a 48-hour chronomodulated infusion in combination with leucovorin and cisplatin: A randomized phase II study in metastatic colorectal cancer

Alfredo Falcone, Giacomo Allegrini, Gianluca Masi, Monica Lencioni, Elisabetta Pfanner, Isa Brunetti, Romano Danesi, Guido Bocci, Mario Del Tacca, Pierfranco Conte

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: The primary objective of this trial was to determine the objective response of two regimens with CDDP administered every 2 weeks immediately before or after an 'optimal' 48-hour chronomodulated infusion of 5-fluorouracil (5-FU) modulated with leucovorin (LV) in metastatic colorectal cancer patients. Secondary endpoints were toxicity, 5-FU and its metabolites, plasma pharmacokinetics and progression-free and overall survival. Methods: Metastatic colorectal cancer patients with measurable disease who were chemotherapy-naive or pretreated only with a 5-FU-bolus-based chemotherapy were eligible for this study. The study was designed as a randomized phase II clinical trial. Results: Eighty-three patients were entered into the study. Forty-two were randomized to CDDP given before 5-FU and 41 to CDDP given after 5-FU. Patient characteristics were similar among the two groups. Toxicities were also similar among the two arms and the most frequent WHO grade III-IV toxicities were stomatitis (14%) and neutropenia (39-50%). Plasma pharmacokinetic profiles of 5-FU and 5-FUH2 were not significantly affected by the sequence of CDDP and 5-FU administration. Antitumor activity was similar in the two arms and was very promising both in pretreated patients (response rate 29%; 95% confidence interval 15-46%) and in chemotherapy-naive patients (response rate 56%, complete response 9%, 95% confidence interval 40-71%). Median survival of the patients with and without pretreatment was 12 and 16 months, respectively. Conclusions: These results do not suggest a sequence dependence of the synergism between CDDP and 5-FU. However, they challenge the need of oxaliplatin to improve 5-FU/LV activity in advanced colorectal cancer. In fact, our results with an 'optimal' 5-FU dose and scheduling are very similar to those obtained with oxaliplatin plus 5-FU/LV. However, only a randomized phase III study will be able to give an answer to the hypotheses raised by this study.

Original languageEnglish
Pages (from-to)28-35
Number of pages8
JournalOncology
Volume61
Issue number1
DOIs
Publication statusPublished - 2001

Keywords

  • 5-Fluorouracil
  • Chronoinfusion
  • Cisplatin
  • Colorectal cancer
  • Randomized study

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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