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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 < .0001) and OS (P = .001) on chronoFLO4. The median OS on chronoFLO4 was 13.8 months (95% CL, 10.4-17.2 months) or 21.1 months (95% CL, 19.0-23.1 months) according to presence or absence of chemotherapy-induced FWL, respectively. CONCLUSIONS: Early onset chemotherapy-induced FWL was an independent predictor of poor TTP and OS only on chronotherapy. Dynamic monitoring to detect early chemotherapy-induced circadian disruption could allow the optimization of rapid chronotherapy and concomitant improvements in safety and efficacy.

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Repositório do Hospital Prof. Doutor Fernando Fonseca  


Innominato, PF -  Giacchetti, S -  Moreau, T -  Bjarnason, GA -  Smaaland, R -  Focan, C -  Garufi, C -  Iacobelli, S -  Tampellini, M -  Tumolo, S -  Carvalho, C -  Karaboué, A -  Poncet, A -  Spiegel, D -  Lévi, F -  International Association for Research on Time in Biology and Chronotherapy (ARTBC) Chronotherapy Group. - 

Id.: 65143261

Idioma: eng  - 

Versión: 1.0

Estado: Final

Palabras claveColorectal neoplasms - 

Tipo de recurso: article  - 

Tipo de Interactividad: Expositivo

Nivel de Interactividad: muy bajo

Audiencia: Estudiante  -  Profesor  -  Autor  - 

Estructura: Atomic

Coste: no

Copyright: sí

: openAccess

Requerimientos técnicos:  Browser: Any - 

Relación: [References] http://onlinelibrary.wiley.com/doi/10.1002/cncr.28072/pdf

Fecha de contribución: 23-mar-2016


* Cancer. 2013 Jul 15;119(14):2564-73
* 1097-0142
* 10.1002/cncr.28072.

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