151751-Najiba-Chargi

259 Systemic therapy: the prospective PLATISMA study INTRODUCTION Head and neck squamous cell carcinomas (HNSCCs) are among the most frequent tumors worldwide. 1 Two-thirds of HNSCC patients present with advanced disease which is treatedwith cisplatin-based chemoradiotherapy (CRT). 2 Acute toxicity of cisplatin, such as nephrotoxicity and ototoxicity, results in dose-reductions, treatment delay or treatment cessation (chemo- therapy dose limiting toxicity, CDLT) in at least 30% of patients. 3–5 CDLTs negatively affect survival because patients receive a suboptimal treatment. 5 In recent years, a relationship between radiologically assessed low skeletal musclemass (SMM) and CDLT has been described for HNSCC. 6–8 A retrospective study in HNSCC patients undergoing CRT showed that patients with low SMM had a 3-fold higher risk of experiencing CDLT (44.3% vs. 13.7%), which resulted in a significantly shorter overall survival than for patients who were able to complete CRT. 7 An explanation for the relationship between low SMM and toxicity might be that hydrophilic drugs, including cisplatin, mainly distribute into the fat-free body mass of which SMM is the largest contributor. 9 Cisplatin is a highly reactive drug and upon administration the drug will bind to tumor DNA causing its anti-cancer effect, but also to tissue causing side effects and lastly to tissue without any pharmacodynamic effect. 10 We hypothesized that this latter com - partment is highly related to SMM. In patients with a low SMM less tissue is available to which cisplatin can bind relatively harmless, but more reactive cisplatin is available to bind to tissue related to toxicity. This might lead to increased CDLTs negatively affecting outcome. The aim of this prospective observational study was to investigate the relationship between SMM and pharmacokinetic (PK) parameters of cisplatin in HNSCC patients. We hypothesized that an altered distribution of cisplatin could explain why patients with low SMM are more prone to experience cisplatin toxicity. 14