VALIDATION OF A NEW INTERACTIVE SOFTWARE MONITORING A CONTROLLED-FLOWINFUSION-PUMP FOR CISPLATIN DOSAGE REGIMEN ADJUSTMENT

Adaptive dosing of cisplatin (CDDP) results in reduced haematological and renal toxicity but it has never been clearly shown that it affects the tumoral response rate. Before undertaking a clinical randomized s tudy of CDDP monitoring versus standard dose, a comparative study was performed between a new software dedicated to the interactive adjustme nts - the AJI software - and the APIS software for clinical pharmacoki netics which incorporates a bayesian procedure and a population inform ation computed according to a three compartment model. CDDP was admini stered by continuous infusion at variable rates with a controlled flow pump during four days in order to reach the target of 1.3 mg/L at the end of the first day, and to maintain this level during the whole tre atment. This study was carried our on two groups of patients. Group I (12 patients; 27 courses) received CDDP with sequential flow rates in order to obtain a population information to be used with AJI. For pati ents in group 2 (14 patients; 26 courses), doses (flows) were adapted in a prospective study using the AJI software two to three times the f irst day, then daily. They could have been adapted (retrospective stud y) after platin pharmacokinetic parameters identification by APIS. The dosage recommendations proposed by APIS the first day, from 12 hours to 24 hours, to reach the target of 1.3 mg/L at 24 hours, and then dai ly up to D4 (AAPT at Di) to maintain this level were compared to those ,which were really administered during the interactive treatment (DA a t Di). There were no statistically significant difference for D2, D4 a nd for the total dose (118.7 +/- 20.1 mg and 118.5 +/- 45.1 mg). The d ifference war statistically significant for D1 and D3 (P < 0.05). The inter-individual variability war less important with AJI (CV = 16.9% f or DA total) than with APIS (CV = 38.0% for ADAPT total). The platin p harmacokinetic parameters identified the first day by APIS were not st atistically different from those identified from the whole treatment f or clearance (5.92 and 5.63 l/d) and Vtotal 87.8 and 93.1 L); the diff erence was statistically significant for Vinitial (34.7 and 42.5 L; P < 0.05) and the terminal half-life (13.1 and 15.5 days; P < 0.05).