A randomized multicenter study of optimal circadian time of vinorelbine combined with chronomodulated 5-fluorouracil in pretreated metastatic breast cancer patients: EORTC trial 05971.
Fiche publication
Date publication
septembre 2008
Auteurs
Membres identifiés du Cancéropôle Est :
Dr COUDERT Bruno
Tous les auteurs :
Coudert B, Focan C, Genet D, Giacchetti S, Cvickovic F, Zambelli A, Fillet G, Chollet P, Amoroso D, Van Der Auwera J, Lentz MA, Marreaud S, Baron B, Gorlia T, Biville F, Levi F
Lien Pubmed
Résumé
Studies in animals synchronized with an alternation of 12 h of light and 12 h of darkness have showed that hematological and systemic toxicities could be reduced if vinorelbine were administered 19 or 23 hours after light onset (HALO), corresponding to 17:00 and 21:00 h in diurnally active humans. This trial aimed to define the least toxic time of vinorelbine administration in metastatic breast cancer patients. Initially, the study treatment consisted of three courses of vinorelbine of 30 mg/m(2)/d on D1 and D6 and chronomodulated 5-fluorouracil of 850 mg/m(2) from D2 to D5 every 21 days. Ninety metastatic breast cancer patients were randomized to receive vinorelbine at one of the eight possible dosing times. Further to the recommendations of the Independent Data Monitoring Committee, the vinorelbine dose was reduced to 25 mg/m(2)/d midway through the study. The primary objective of the study was detection of the least toxic time based on the incidence of grade 3-4 (G3-4) neutropenia. To show a significant result, the 90% confidence interval width of the least toxic time had to be
Référence
Chronobiol Int. 2008 Sep;25(5):680-96.