PURPOSE: Although body composition has emerged as an important predictor of drug efficacy and toxicity, explanations for this association are unclear. Our goal was to investigate relationships between lean body mass (LBM), liver size/function and epirubicin pharmacokinetics (PK) and toxicity. METHODS: Data from a clinical study (n = 24) of patients with breast cancer receiving adjuvant intravenous FE(100)C chemotherapy were used to examine relationships between LBM, liver size, and epirubicin clearance. Muscle tissue and liver mass were measured by analysis of computerized tomography cross-sectional images, and an extrapolation of muscle mass to total LBM compartment was employed. Population PK analysis of epirubicin was undertaken to test effects of body composition on epirubicin clearance and area under the curve (AUC). RESULTS: Estimated LBM was extremely variable in this cohort ranging from 32.9 to 67.3 kg. LBM was associated with neutrophil nadir (r = 0.5, P = 0.023), and mean LBM was lower for patients presenting with toxicity compared to those where toxicity was absent (41.6 vs. 56.2 kg, P = 0.002); 33% of variance in clearance was explained by LBM and aspartate aminotransferase (AST). Liver mass was not related to epirubicin clearance likely due to larger livers presenting with larger fat content, but liver attenuation (degree of fat infiltration) and AST were associated with AUC. CONCLUSION: To our knowledge, this is the first study to examine relationships between LBM, liver mass/function and epirubicin PK and toxicity. This exploratory work investigates the notion of organs and tissues having distinctive contributions to the distribution and metabolism of antineoplastic drugs.
PURPOSE: Although body composition has emerged as an important predictor of drug efficacy and toxicity, explanations for this association are unclear. Our goal was to investigate relationships between lean body mass (LBM), liver size/function and epirubicin pharmacokinetics (PK) and toxicity. METHODS: Data from a clinical study (n = 24) of patients with breast cancer receiving adjuvant intravenous FE(100)C chemotherapy were used to examine relationships between LBM, liver size, and epirubicin clearance. Muscle tissue and liver mass were measured by analysis of computerized tomography cross-sectional images, and an extrapolation of muscle mass to total LBM compartment was employed. Population PK analysis of epirubicin was undertaken to test effects of body composition on epirubicin clearance and area under the curve (AUC). RESULTS: Estimated LBM was extremely variable in this cohort ranging from 32.9 to 67.3 kg. LBM was associated with neutrophil nadir (r = 0.5, P = 0.023), and mean LBM was lower for patients presenting with toxicity compared to those where toxicity was absent (41.6 vs. 56.2 kg, P = 0.002); 33% of variance in clearance was explained by LBM and aspartate aminotransferase (AST). Liver mass was not related to epirubicin clearance likely due to larger livers presenting with larger fat content, but liver attenuation (degree of fat infiltration) and AST were associated with AUC. CONCLUSION: To our knowledge, this is the first study to examine relationships between LBM, liver mass/function and epirubicin PK and toxicity. This exploratory work investigates the notion of organs and tissues having distinctive contributions to the distribution and metabolism of antineoplastic drugs.
Authors: Shlomit Strulov Shachar; Allison M Deal; Marc Weinberg; Grant R Williams; Kirsten A Nyrop; Karteek Popuri; Seul Ki Choi; Hyman B Muss Journal: Clin Cancer Res Date: 2017-01-31 Impact factor: 12.531
Authors: Shlomit Strulov Shachar; Allison M Deal; Marc Weinberg; Kirsten A Nyrop; Grant R Williams; Tomohiro F Nishijima; Julia M Benbow; Hyman B Muss Journal: Clin Cancer Res Date: 2016-08-03 Impact factor: 12.531
Authors: C Narjoz; A Cessot; A Thomas-Schoemann; J L Golmard; O Huillard; P Boudou-Rouquette; A Behouche; F Taieb; J P Durand; A Dauphin; R Coriat; M Vidal; M Tod; J Alexandre; M A Loriot; F Goldwasser; B Blanchet Journal: Invest New Drugs Date: 2014-10-25 Impact factor: 3.850
Authors: S Gérard; D Bréchemier; A Lefort; S Lozano; G Abellan Van Kan; T Filleron; L Mourey; C Bernard-Marty; M E Rougé-Bugat; V Soler; B Vellas; M Cesari; Y Rolland; L Balardy Journal: J Nutr Health Aging Date: 2016 Impact factor: 4.075