A BAYESIAN DOSING METHOD FOR CARBOPLATIN GIVEN BY CONTINUOUS-INFUSIONFOR 120 H

Carboplatin (CBDCA), an analogue of cisplatin, exhibits reduced toxici ty but wide interpatient variability of its pharmacokinetic parameters . Individualization of the CBDCA dose is therefore necessary. Although various formulas have been developed for this purpose, major side eff ects have been reported on CBDCA administration by short-term infusion (0.5 or 1h). We therefore propose a new schedule of CBDCA administrat ion. Instead of a dosing method based on the estimation of renal funct ion when a classic administration schedule is used, we propose a pharm acokinetic dosing method (Bayesian method), whereby CBDCA is given by continuous infusion for 120 h. First, CBDCA was given to 21 patients t o determine the population pharmacokinetic parameters of carboplatin. Then, on the basis of total platinum plasma concentration measurements and Bayesian estimation of pharmacokinetic parameters, it was possibl e to individualize the CBDCA dose within the first 24 h of the infusio n. This new protocol for CBDCA administration was evaluated in 36 new patients (60 courses). Three theoretical end points at the end of the infusion were considered. For a given theoretical end point, 20 course s were taken into account. The theoretical end points (i.e., 1, 1.5, a nd 1.8 mg/l) were compared with the concentrations measured at the end of the infusion, which were 0.99 +/- 0.10, 1.41 +/- 0.13, and 1.72 +/ - 0.20 mg/l, respectively. This Bayesian dosing method can easily be u sed in clinical practice, and the determination of predictive performa nces has shown that the method is precise and unbiased. With no more t oxicity or practical difficulties than those produced by other methods , and with acceptable tolerance, it was possible to reach a median dos e that was 20% higher than the usual dose (484 +/- 190 mg/m(2) as comp ared with 400 mg/m(2)). In conclusion, this new schedule of CBDCA admi nistration appears to be interesting in terms of tolerance. However, n ew studies are required to confirm that this new scheme leads to equal or better efficacy than the classic protocol.