151751-Najiba-Chargi

266 CHAPTER 14 DISCUSSION In this prospective observational study, we investigated the relationship between cisplatin PK and SMM. As expected, we found an association between cisplatin PK, especially bound cisplatin, and SMM. A pharmacokinetic simulation showed that patients with low SMM reached higher concentrations of bound cisplatin, which could be an explanation for the higher toxicity in this patient group. The higher concentration of bound cisplatin could be seen as a reflection of the smaller volume of distribution. Because of this smaller volume, less tissue is available where cisplatin can distribute to and bind with, without inducing toxicity. In this study no data was available on the concentration of bound cisplatin in tissue. We expected that patients experiencing CDLTs would have higher maximum concentrations of bound cisplatin in plasma, however we did not find a correlation between these two parameters. No relationship was found between DLTs and a low LSMI, which was seen in previous studies, most likely explained by the low number of patients to study this association. 7,24 Although we found a relationship between cisplatin PK and SMM, there was also a significant relationship between cisplatin PK and the other body composition descriptors. Based on the findings in this study, both SMM and the other body composition descriptors predict cisplatin pharmacokinetics. We also found SMM to be correlated with weight, which might explain why cisplatin pharmacokinetics is also related to weight and FFM. CONCLUSION HNSCC patients with low SMM reach higher bound cisplatin concentrations, although no cor - relation was seen between cisplatin DLT and low SMM. Further studies which examine the level of bound cisplatin at the end organs are needed to further clarify the relationship between low SMM and cisplatin DLTs in HNSCC patients.