Trial reportClinical pharmacokinetics2007
Population pharmacokinetics of the BEACOPP polychemotherapy regimen in Hodgkin's lymphoma and its effect on myelotoxicity.
Trial report in Clinical pharmacokinetics, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
8 citing papers in PubMed, 20 citations in OpenAlex.
- Age-Dependent Pharmacokinetics of Doxorubicin in Children with Cancer.Clinical pharmacokinetics · 2015Trial
- Pediatric doxorubicin exposure induces persistent pathological changes in mice.Toxicology and applied pharmacology · 2025Article
- Cytotoxic mechanisms of doxorubicin at clinically relevant concentrations in breast cancer cells.Cancer chemotherapy and pharmacology · 2022Review
- Evaluation for pharmacokinetic exposure of cytotoxic anticancer drugs in elderly patients receiving (R-)CHOP therapy.Scientific reports · 2021Article
- Effects of ranolazine in a model of doxorubicin-induced left ventricle diastolic dysfunction.British journal of pharmacology · 2017Article
- Population pharmacokinetics of doxorubicin and doxorubicinol in patients diagnosed with non-Hodgkin's lymphoma.British journal of clinical pharmacology · 2016Article
- Fundamentals of population pharmacokinetic modelling: validation methods.Clinical pharmacokinetics · 2012Review
- Population pharmacokinetics and pharmacodynamics for treatment optimization in clinical oncology.Clinical pharmacokinetics · 2008Review
Corrections and comments
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Authors and funding
15 authors at 7 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectiveThe 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
designThree 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.
resultsThe 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.
conclusionThe 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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