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Clinical Pharmacokinetics
Published in: Clinical Pharmacokinetics 4/2007

01-04-2007 | Original Research Article

Population Pharmacokinetics of the BEACOPP Polychemotherapy Regimen in Hodgkin’s Lymphoma and its Effect on Myelotoxicity

Authors: Stefan Wilde, Alexander Jetter, Stephan Rietbrock, Dirk Kasel, Andreas Engert, Andreas Josting, Beate Klimm, Georg Hempel, Stefanie Reif, Ulrich Jaehde, Ute Merkel, Dagmar Busse, Matthias Schwab, Volker Diehl, Prof. Dr Uwe Fuhr

Published in: Clinical Pharmacokinetics | Issue 4/2007

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Abstract

Background and objective

The BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisone) chemotherapy regimen for the treatment of advanced Hodgkin’s lymphoma has a superior outcome, but its toxicity (mainly haematotoxicity) is pronounced and highly variable. The present study was conducted to address the role of pharmacokinetics in individual toxicity.

Study design

Three plasma samples and a 24-hour urine collection for day 1 of the first three cycles of chemotherapy were analysed in 30 patients, and the pharmacokinetic parameters of the respective drugs were estimated by population pharmacokinetic methods (nonlinear mixed-effects model [NONMEM] software). Demographic data, doses and durations of infusion were also recorded. The effect of these parameters on platelet counts was estimated by analysis of covariance using a general linear model.

Results

The pharmacokinetic parameters and respective covariates were similar to the published data. The body surface area, peak concentrations of etoposide, urinary recovery of dechloroethylcyclophosphamide (formed by cytochrome P450 [CYP] 3A4) relative to the cyclophosphamide dose and number of cycles had a significant effect on toxicity. These factors explained 37% of the interindividual variability in the change in platelet counts from day 1 to day 8 of each cycle.

Conclusion

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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Metadata
Title
Population Pharmacokinetics of the BEACOPP Polychemotherapy Regimen in Hodgkin’s Lymphoma and its Effect on Myelotoxicity
Authors
Stefan Wilde
Alexander Jetter
Stephan Rietbrock
Dirk Kasel
Andreas Engert
Andreas Josting
Beate Klimm
Georg Hempel
Stefanie Reif
Ulrich Jaehde
Ute Merkel
Dagmar Busse
Matthias Schwab
Volker Diehl
Prof. Dr Uwe Fuhr
Publication date
01-04-2007
Publisher
Springer International Publishing
Published in
Clinical Pharmacokinetics / Issue 4/2007
Print ISSN: 0312-5963
Electronic ISSN: 1179-1926
DOI
https://doi.org/10.2165/00003088-200746040-00005

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