Prediction of survival by neutropenia according to delivery schedule of oxaliplatin-5-fluorouracil-leucovorin for metastatic colorectal cancer in a randomized international trial (EORTC 05963)

Pasquale F. Innominato, Sylvie Giacchetti, Thierry Moreau, Rune Smaaland, Christian Focan, Georg A. Bjarnason, Carlo Garufi, Stefano Iacobelli, Marco Tampellini, Salvatore Tumolo, Carlos Carvalho, Abdoulaye Karaboué, Francis Lévi

Research output: Contribution to journalArticlepeer-review

Abstract

Circadian clocks control cellular proliferation and drug metabolism over the 24h. However, circadian chronomodulated chemotherapy with 5-fluorouracil, leucovorin, and oxaliplatin (chronoFLO4) offered no survival benefit as compared with the nontime-stipulated FOLFOX2, in an international randomized trial involving patients with previously untreated metastatic colorectal cancer (EORTC 05963). The authors hypothesized that treatment near maximum tolerated dose could disrupt circadian clocks thus impairing the efficacy of chronoFLO4 but not of FOLFOX2. Patients with available data (N=556) were categorized into three subgroups according to the worst grade (G) of neutropenia experienced during treatment. Distinct multivariate models with time-dependent covariates were constructed for each treatment schedule. Neutropenia incidence (all grades) was 33% on chronoFLO4 and 61% on FOLFOX2 (p

Original languageEnglish
Pages (from-to)586-600
Number of pages15
JournalChronobiology International
Volume28
Issue number7
DOIs
Publication statusPublished - Aug 2011

Keywords

  • Chemotherapy
  • Chronotherapy
  • Circadian
  • Colorectal cancer
  • Neutropenia
  • Prognostic factor

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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