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)

Circadian clocks control cellular proliferation and drug metabolism over the 24 h. However, circadian chronomodulated chemotherapy with 5-fluorouracil, leucovorin, and oxaliplatin (chronoFLO4) offered no survival benefit as compared with the non-time-stipulated FOLFOX2, in an international randomize...

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Bibliographic Details
Published in:Chronobiology international 2011-08, Vol.28 (7), p.586-600
Main Authors: Innominato, Pasquale F., Giacchetti, Sylvie, Moreau, Thierry, Smaaland, Rune, Focan, Christian, Bjarnason, Georg A., Garufi, Carlo, Iacobelli, Stefano, Tampellini, Marco, Tumolo, Salvatore, Carvalho, Carlos, Karaboué, Abdoulaye, Lévi, Francis
Format: Article
Language:English
Subjects:
Adult
Aged
Antineoplastic Agents - administration & dosage
Antineoplastic Agents - therapeutic use
Antineoplastic Combined Chemotherapy Protocols - administration & dosage
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Biological Clocks - physiology
Chemotherapy
Chronotherapy
Circadian
Circadian Rhythm - physiology
Colorectal cancer
Colorectal Neoplasms - drug therapy
Colorectal Neoplasms - pathology
Disease-Free Survival
Drug Administration Schedule
Female
Fluorouracil - administration & dosage
Fluorouracil - therapeutic use
Humans
Leucovorin - administration & dosage
Leucovorin - therapeutic use
Male
Maximum Tolerated Dose
Middle Aged
Neoplasm Metastasis
Neutropenia
Neutropenia - chemically induced
Organoplatinum Compounds - administration & dosage
Organoplatinum Compounds - therapeutic use
Prognosis
Prognostic factor
Survival Analysis
Treatment Outcome
Young Adult
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Summary:Circadian clocks control cellular proliferation and drug metabolism over the 24 h. However, circadian chronomodulated chemotherapy with 5-fluorouracil, leucovorin, and oxaliplatin (chronoFLO4) offered no survival benefit as compared with the non-time-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 
ISSN:0742-0528
1525-6073
DOI:10.3109/07420528.2011.597532