The results show that the individual pharmacokinetics of BEACOPP drugs are an important link between dosage and toxicity. Accordingly, individualisation of treatment based on pharmacokinetics may result in more uniform toxicity. Individualisation may also allow escalation of the mean dose, which is probably related to better efficacy. As a consequence of the present study, infusion rates should be standardised, and the potential of a dose reduction in the first cycle and of CYP3A4 phenotyping should be addressed in clinical studies.

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BACKGROUND/AIMS: The BEACOPP chemotherapy regimen (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) used for Hodgkin's disease has a superior outcome, but pronounced and variable toxicity (mainly hematotoxicity). The present study was carried out to identify the impact of individual pharmacokinetics on the degree of hematotoxicity. METHODS:In 30 patients treated with BEACOPP, three plasma samples and urine collected over 24 h on the first day of the first three cycles were analysed. Demographic data, doses, infusion times and blood cell counts were recorded. Pharmacokinetics parameters of the antineoplastic agents were estimated with population pharmacokinetic methods (NONMEM software); factors with potential influence on platelet counts were identified by ANOVA using a general linear model.RESULTS: Pharmacokinetic parameters could be calculated successfully for cyclophosphamide, etoposide, doxorubicin, and procarbazine. Creatinine clearance, infusion rates of etoposide and urinary excretion rates of N-dechloroethylcyclo-phosphamide and carboxycyclophosphamide had a significant effect on the decrease in platelet count from day 1 to day 8 of each cycle, explaining 46% of the interindividual variability of this parameter.CONCLUSIONS: Individualization of treatment based on the factors identified here may decrease toxicity of the BEACOPP polychemotherapy regimen.