Fatigue and weight loss predict survival on circadian chemotherapy for metastatic colorectal cancer

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

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND Chemotherapy-induced neutropenia has been associated with prolonged survival selectively in patients on a conventional schedule (combined 5-fluorouracil, leucovorin, and oxaliplatin [FOLFOX2]) but not on a chronomodulated schedule of the same drugs administered at specific circadian times (chronoFLO4). The authors hypothesized that the early occurrence of chemotherapy-induced symptoms correlated with circadian disruption would selectively hinder the efficacy of chronotherapy. METHODS Fatigue and weight loss (FWL) were considered to be associated with circadian disruption based on previous data. Patients with metastatic colorectal cancer (n = 543) from an international phase 3 trial comparing FOLFOX2 with chronoFLO4 were categorized into 4 subgroups according to the occurrence of FWL or other clinically relevant toxicities during the initial 2 courses of chemotherapy. Multivariate Cox models were used to assess the role of toxicity on the time to progression (TTP) and overall survival (OS). RESULTS The proportions of patients in the 4 subgroups were comparable in both treatment arms (P =.77). No toxicity was associated with TTP or OS on FOLFOX2. The median OS on FOLFOX2 ranged from 16.4 (95% confidence limits [CL], 7.2-25.6 months) to 19.8 months (95% CL, 17.7-22.0 months) according to toxicity subgroup (P =.45). Conversely, FWL, but no other toxicity, independently predicted for significantly shorter TTP (P

Original languageEnglish
Pages (from-to)2564-2573
Number of pages10
JournalCancer
Volume119
Issue number14
DOIs
Publication statusPublished - Jul 15 2013

Keywords

  • chemotherapy
  • circadian
  • colorectal cancer
  • prognostic factor
  • toxicity

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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