Annals of Oncology 13:280-285, 2002
© 2002 European Society for Medical Oncology
Influence of alternate sequences of epirubicin and docetaxel on the pharmacokinetic behaviour of both drugs in advanced breast cancer
1Servizio di Farmacologia e Neuroscienze, Laboratorio di Farmacologia Tossicologica and 2Dipartimento di Oncologia Medica I, Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
Received 2 May 2001; revised 20 July 2001; accepted 23 August 2001.
Background
Previously we observed a pharmacokinetic interference of epirubicin elimination when paclitaxel is given in combination in a sequence-dependent manner (i.e. when paclitaxel is administered as first drug). The aim of this study was to determine whether these sequence-dependent pharmacological effects were also evident when epirubicin was combined with docetaxel.
Patients and methods
Patients who received epirubicin 75 mg/m2 or 90 mg/m2 as an intravenous bolus followed immediately by docetaxel 70 mg/m2 or 80 mg/m2 over a 1-h infusion, or the opposite sequence, every 3 weeks were eligible for this study. The pharmacokinetics of docetaxel, epirubicin and its metabolites were studied at the first and second cycle of treatment. Pharmacokinetic data were normalised to the lower dose of each drug. Toxicity was recorded at nadir and graded according to National Cancer Institute Common Toxicity Criteria.
Results
Twelve consecutive patients, each acting as their own control, entered the study. The sequence of drug administration of docetaxel and epirubicin did not affect the pharmacokinetics of the parent anthracycline. Statistically significant lower glucuronidation metabolism of epirubicin was observed in patients who received docetaxel before epirubicin. The pharmacokinetics of docetaxel were not influenced by the sequence of drug administration. No difference in haematological and non-haematological toxicity was observed in the two sequences of treatment.
Conclusions
The pharmacokinetics of the parent anthracycline and of docetaxel were similar between the two schemes of treatment. The metabolic variations observed, i.e. differences in the plasma levels of epirubicin glucuronides, seem not to have clinical relevance.
Key words: combination treatment, docetaxel, epirubicin, pharmacokinetics
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