151751-Najiba-Chargi

258 CHAPTER 14 ABSTRACT Background Locally advanced head and neck squamous cell carcinoma (HNSCC) is commonly treated with cisplatin-based chemoradiotherapy (CRT). Cisplatin is associated with severe toxicity, which negatively affects survival. In recent years, a relationship between low skeletal muscle mass (SMM) and toxicity has been described. This increased toxicity may be related to altered cisplatin distribution and binding in the fat-free body mass of which SMM is the largest con- tributor. This study aims to investigate the association between cisplatin pharmacokinetics and SMM in HNSCC patients. Material and methods We performed a prospective observational study in HNSCC patients treated with CRT. Patients received standard-of-care chemotherapy with three cycles of cisplatin at a dose of 100 mg/m 2 per cycle. Quantitative data on SMM, measured on computed tomography scans and cisplatin pharmacokinetics (total and ultrafiltrable plasma concentrations) were collected, as well as data on toxicity. Results In total, 45 evaluable patients were included in the study. A large proportion of the study population had a low SMM (46.7%). The majority of patients (57.8%) experienced cisplatin dose limiting toxicities. Pharmacokinetic analysis showed a relationship between cisplatin pharmacokinetics and SMM ( p <0.005). In a simulation, patients with a low SMM (<25.8 kg) were predicted to reach higher bound cisplatin concentrations. Conclusion We found an association between cisplatin pharmacokinetics and SMM, however this rela - tionship was also seen between cisplatin pharmacokinetics and other body composition descriptors.