151751-Najiba-Chargi

265 Systemic therapy: the prospective PLATISMA study For the final model a simulation was performed in which the effects of different SMMs on the PK of cisplatin were predicted. Plots of the population predicted cisplatin concentrations vs time derived from this simulation are shown in figure 4, which shows that patients with a lower SMM are predicted to reach higher concentrations of bound cisplatin. Figure 3. Population predicted cisplatin concentrations versus time. The left panel shows predicted free cisplatin concentrations, and the right panel shows predicted bound cisplatin concentrations. Simula - tions were performed using themodel inwhich skeletal musclemass was added as covariate on clearance of free cisplatin, and on clearance and volume of distribution of bound cisplatin. Skeletal muscle mass was simulated around the threshold of 25.8 kg for a low skeletal muscle mass, with corresponding body surface area and thus dose given. Figure 4. Correlation between dose limiting toxicities (DLTs) of cisplatin and the maximum plasma con - centration (Cmax) of bound cisplatin (Wilcoxon rank sum test; p=0.85) Lastly, the correlation between CDLTs and themaximumplasma concentration (C max ) of bound cisplatin was examined. One subject was excluded in this analysis, because this subject re - ceived a lower dose of cisplatin compared to the other patients. No correlation between CDLTs and the C max of bound cisplatin was found (Wilcoxon rank sum test; p =0.85), which is illustrated by the boxplots in figure 6. 14