151751-Najiba-Chargi

261 Systemic therapy: the prospective PLATISMA study (1) (2) (3) (4) (5) (3) (1) (2) (3) (4) (5) (4) In these equations BMI is the body mass index (weight/height 2 ; weight in kg and height in m). CISPLATIN BIOANALYSIS Plasma and ultrafiltrable (using a filter of 30 kDa) samples were collected from patients at different time points (pre-dose, end of infusion and 1 hour, 3 hours, 7 hours and 20 hours after end of infusion) during the first cycle of cisplatin. Both total and ultrafiltrable plasma concentrations of platinumweremeasured by inductively coupled plasma-mass spectrometry (ICP-MS) by a previously described method. 20 For simplification, the terms free and bound cisplatin are used throughout to denote ultrafilterable and non-ultrafilterable platinum spe- cies, respectively. CISPLATIN RELATED TOXICITY Toxicity was scored according to the Common Terminology Criteria for Adverse Events (CTCAE) guidelines, version 4.03. 21 CDLT was defined as any toxicity resulting in cisplatin dose-reduc- tion of ≥50%, a treatment delay of ≥4 days or cessation of cisplatin after the first or second cycle of therapy. PHARMACOKINETIC ANALYSIS For description of cisplatin PK a two-compartment model for free cisplatin, followed by one compartment for protein-bound cisplatin was used, as previously described by Urien et al . 14 Clearance of free cisplatin was considered negligible compared to binding to proteins and, therefore, not included in the model. More detailed information about the PK model can be found in the Supplementary materials. The body composition descriptors weight, SMM, FFM, and BSA were separately evaluated as covariates on clearance of free cisplatin (CL free ), volume of distribution of free cisplatin (V free ), intercompartmental clearance (Q), and volume of distribution of the peripheral compartment (V p ) of free cisplatin, clearance of bound cisplatin (CL bound ) and volume of distribution of bound cisplatin (V bound ). The body composition descriptors were evaluated using equation 5: (1) (2) (3) (4) (5) (5) Where θ i represents the parameter estimate for individual i , θ pop represents the typical pa- rameter estimate for the population, and k represents the exponent. Based on the theory of allometric scaling the exponent was fixed to 0.75 for evaluation of clearance, and to 1 for volume of distribution 22 . For both clearance and volume of distribu - tion the exponent was also estimated. The glomerular filtration rate (GFR; calculated using 14