Influence of the skeletal muscle index on pharmacokinetics and toxicity of fluorouracil. (8th August 2022)

• Record Type: Journal Article
• Authors: Schmulenson, Eduard; Zimmermann, Nigina; Müller, Lothar; Kapsa, Stefanie; Sihinevich, Iryna; Jaehde, Ulrich
• Is Part Of: Cancer medicine. Volume 12:Number 3(2023)
• Page Start: 2580
• Page End: 2589
• Publication Date: 2022-08-08
• Subjects: body composition -- fluorouracil -- pharmacokinetics -- skeletal muscle index; 616.994005
• DOI: 10.1002/cam4.5118
• Languages: English
• ISSNs: 2045-7634

Abstract

Abstract: Background: The body composition of patients has been associated with tolerability and effectiveness of anticancer therapy. This study aimed to assess the influence of the skeletal muscle index (SMI) on the pharmacokinetics and toxicity of fluorouracil. Methods: Patients treated in an oncological practice with fluorouracil‐based chemotherapy and undergoing therapeutic drug monitoring were retrospectively investigated. Computed tomography images were analyzed to measure abdominal skeletal muscle areas in Hounsfield units for the psoas major muscle, back and total skeletal muscle to determine the SMI. For the latter, an automated segmentation method was used additionally. SMI measures were tested as covariates on fluorouracil clearance in a population pharmacokinetic model. Furthermore, regression analyses were performed to analyze the influence of SMI measures on the probability of clinically relevant adverse events (CTCAE grades ≥ 2). Results: Fluorouracil plasma concentrations of 111 patients were available. Covariate analyses showed significant improvements of the model fit by all SMI measures. However, interindividual variability of fluorouracil clearance was only slightly reduced, whereas the SMI of the back muscle showed the largest reduction (−1.1 percentage points). Lower SMI values of the back muscle increased the probability for polyneuropathy and lower SMI of the psoas increased the probability for fatigue. Conclusions: Our results suggest that pharmacokinetics and toxicity of fluorouracil may be associated with specific SMI measures which deserve further investigation. Abstract : In sarcopenic cancer patients, the influence of altered body composition on clinical outcome of anticancer drug therapy is still not completely understood. Results from population pharmacokinetic modeling and logistic regression suggest that skeletal muscle index (SMI) measures may be associated with clearance of fluorouracil (5FU) and the occurrence of fatigue and polyneuropathy, respectively. These relationships deserve further investigation.