Total Body Water predicts 5-FU plasma concentration after the first cure of chemotherapy

Abstract

2107 Background: Plasma concentrations of cytostatic drugs ranging within a narrow therapeutic index should be obtained to ensure maximal efficacy and minimal toxicity. The aim of this study was to demonstrate that plasma 5-FU (an hydrophilic drug) concentrations could be predicted from estimates of body water spaces. Methods: Body composition was assessed in 35 patients suffering from digestive cancer after the first cure of chemotherapy using 5-FU. 5-FU was administered as FOLFOX, FOLFIRI or De Gramont (LV5-FU2) protocols. Initial doses were adapted to body surface area. Body composition was estimated from Total Body Water (TBW), Extra Cellular Water (ECW) or Intra Cellular Water (ICW) (multifrequency bioelectrical impedance analysis), Fat Free Mass (FFM) (combination of TBW and body density measured by plethysmography ). 5-FU plasma concentrations were determined by HPLC. Results: Pharmacokinetics parameters (steady state plasmatic concentration, AUC) of 5-FU did not differ between chemotherapy protocols. Plasma 5-FU concentration was correlated with body weight, BMI, TBW, ECW, and FFM. It did not correlate with fat mass. After stepwise multiple regression, only TBW was correlated with 5-FU plasma concentration (p = 0.031; Concentration (ng/ml) = -6.082 x TBW (kg) +666). Similarly clairance of 5-FU was correlated to TBW, ECW, ICW, FFM. After stepwise regression, only TBW predicted clairance. Conclusions: Despite an initial adaptation of 5-FU doses, plasma concentrations were correlated to TBW which could be used as an easy indicator to adapt the doses. Performing BIA is easy. It takes only a few minutes to measure impedances from surface electrodes attached to right hand and foot. Supported by Comité Départemental de Maine et Loire et de la Mayenne, la Ligue Nationale Contre le Cancer. No significant financial relationships to disclose.