Time to Definitive Health-Related Quality of Life Score Deterioration in Patients with Resectable Metastatic Colorectal Cancer Treated with FOLFOX4 versus Sequential Dose-Dense FOLFOX7 followed by FOLFIRI: The MIROX Randomized Phase III Trial.
OBJECTIVE
We previously showed that a sequential chemotherapy with dose-dense oxaliplatin (FOLFOX7) and irinotecan (FOLFIRI; irinotecan plus 5-fluorouracil/leucovorin) is not superior to FOLFOX4 in patients at advanced stage of colorectal cancer with liver metastases. Here we aimed to determine whether time to health-related quality of life (HRQoL) score definitive deterioration (TUDD) differs by study arm.


METHODS
HRQoL was evaluated using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 at baseline and every 4 cycles until the end of the study or death. Functional scale, symptom scale, global health status, and financial difficulties were analyzed. The TUDD was defined as the time interval between randomization and the first decrease in HRQoL score ≥ 5-point with no further improvement in HRQoL score ≥ 5 points or any further HRQoL data. TUDD was estimated using the Kaplan-Meier method and the long-rank test. Cox regression analyses were used to identify HRQoL items influencing TUDD. Sensitivity analyses were done using a multiple imputation method and different definitions of TUDD.


RESULTS
Of the 284 patients, 171 (60.2%) completed HRQoL questionnaires. Cox multivariate analysis showed no statistically significant difference in TUDD for most of the QLQ-C30 scales between treatments. Patients with dyspnea and those without symptoms at baseline had a significantly longer TUDD when there was a delay >12 months between diagnosis of the primary tumor and metastases (HR 0.48 [0.26-0.89]) and when there was diarrhea (HR 0.59 [0.36-0.96]), respectively.


CONCLUSIONS
This study shows that TUDD does not differ significantly according to type of treatment. The TUDD method produces meaningful longitudinal HRQoL results that may facilitate effective clinical decision making in patients with mCRC.


BACKGROUND
ClinicalTrials.gov NCT00268398.
National clinical research Platform for Quality of life in Oncology, Marseille, France.|Public health laboratory, College of Medicine, Marseille, France.
Zeinab
Z
Hamidou
Saint-Antoine Hospital, Department of Medical Oncology, Paris, France.
Benoist
B
Chibaudel
Centre Hospitalier Régional Universitaire, Claude Huriez Hospital, Service of Medical Oncology, Lille, France.
Mohamed
M
Hebbar
Groupe Coopérateur Multidisciplinaire en Oncologie (GERCOR), Paris, France.
Marine
M
Hug de Larauze
Saint-Antoine Hospital, Department of Medical Oncology, Paris, France.
Thierry
T
André
Institut Mutualiste Montsouris, Department of Medical Oncology, Paris, France.
Christophe
C
Louvet
Groupe Coopérateur Multidisciplinaire en Oncologie (GERCOR), Paris, France.
David
D
Brusquant
Saint-Antoine Hospital, Department of Medical Oncology, Paris, France.
Marie-Line
ML
Garcia-Larnicol
Centre Hospitalier Régional Universitaire, Claude Huriez Hospital, Service of Medical Oncology, Lille, France.
Aimery
A
de Gramont
National clinical research Platform for Quality of life in Oncology, Marseille, France.|University Hospital of Besançon, Methodology and quality of life unit in oncology (EA3181), Besançon, France.
Franck
F
Bonnetain
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D011788:Quality of Life; D016896:Treatment Outcome
D009944:Organoplatinum Compounds; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin