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

2013Journal article Open access
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dc.contributor.authorInnominato, PF
dc.contributor.authorGiacchetti, S
dc.contributor.authorMoreau, T
dc.contributor.authorBjarnason, GA
dc.contributor.authorSmaaland, R
dc.contributor.authorFocan, C
dc.contributor.authorGarufi, C
dc.contributor.authorIacobelli, S
dc.contributor.authorTampellini, M
dc.contributor.authorTumolo, S
dc.contributor.authorCarvalho, C
dc.contributor.authorKaraboué, A
dc.contributor.authorPoncet, A
dc.contributor.authorSpiegel, D
dc.contributor.authorLévi, F
dc.contributor.authorInternational Association for Research on Time in Biology and Chronotherapy (ARTBC) Chronotherapy Group.
dc.date.accessioned2016-03-21T12:10:19Z
dc.date.available2016-03-21T12:10:19Z
dc.date.issued2013
dc.description.abstractBACKGROUND: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.pt_PT
dc.identifier.citationCancer. 2013 Jul 15;119(14):2564-73pt_PT
dc.identifier.doi10.1002/cncr.28072.pt_PT
dc.identifier.issn1097-0142
dc.identifier.urihttp://hdl.handle.net/10400.10/1574
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherthe American Cancer Societypt_PT
dc.relation.publisherversionhttp://onlinelibrary.wiley.com/doi/10.1002/cncr.28072/pdfpt_PT
dc.subjectColorectal neoplasmspt_PT
dc.subjectChemotherapypt_PT
dc.subjectWeight Losspt_PT
dc.subjectFatiguept_PT
dc.subjectDisease progressionpt_PT
dc.subjectNeoplasias colorrectaispt_PT
dc.subjectQuimioterapiapt_PT
dc.subjectPerda de pesopt_PT
dc.subjectFadigapt_PT
dc.subjectProgressão da doençapt_PT
dc.titleFatigue and weight loss predict survival on circadian chemotherapy for metastatic colorectal cancerpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.conferencePlaceNew Yorkpt_PT
oaire.citation.endPage2573pt_PT
oaire.citation.startPage2564pt_PT
oaire.citation.titleCancerpt_PT
oaire.citation.volume119pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT

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