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Comparative Effects of Paclitaxel and Docetaxel on the Metabolism and Pharmacokinetics of Epirubicin in Breast Cancer Patients

From the Pharmacotoxicology Laboratory, Department of Preclinical Oncology, and Department of Medical Oncology I, Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy.

Address reprint requests to Marco Venturini, MD, Divisione di Oncologia Medica I, Istituto Nazionale per la Ricerca sul Cancro, L.go R. Benzi,10, 16132 Genova, Italy; email mventur{at}hp380.ist.unige.it

PURPOSE: To investigate whether paclitaxel and docetaxel influence the pharmacokinetics and metabolism of epirubicin.

PATIENTS AND METHODS: We studied the pharmacokinetics and biotransformation patterns of epirubicin in 27 cycles and 20 breast cancer patients. Four patients received epirubicin alone 90 mg/m² by intravenous (IV) bolus; eight patients received the same dose of epirubicin followed immediately by paclitaxel 175 mg/m² in a 3-hour infusion; the other eight patients received epirubicin 90 mg/m² followed immediately by docetaxel 70 mg/m² in a 1-hour infusion. Epirubicin and its metabolites, epirubicinol (EOL) and 7-deoxydoxorubicinone (7d-Aone), were identified by high-pressure liquid chromatography.

RESULTS: No pharmacokinetic interaction between the parent compound epirubicin and taxanes was detected. Conversely, a significant effect on epirubicin metabolism by both paclitaxel and docetaxel was found. Epirubicin given with paclitaxel or docetaxel yielded areas under the plasma concentration-time curves (AUC) for 7d-Aone 1.7-fold and 1.9-fold higher (P < .05), respectively, than epirubicin alone. The appearance of two polar metabolites sensitive to glucuronidase was also significantly greater in both taxane groups. Quantitatively different metabolic rates and patterns for EOL were observed in the paclitaxel and docetaxel combinations. The EOL AUC after paclitaxel treatment (1,521 ± 150 ng/mL*h) was significantly higher (P < .01) than the corresponding values after epirubicin administered either as a single agent (692 ± 46 ng/mL*h) or in combination with docetaxel (848 ± 237 ng/mL*h).

CONCLUSION: There is no apparent pharmacokinetic interaction between the parent compound epirubicin and paclitaxel or docetaxel. A different pattern of interaction between these taxanes and epirubicin metabolism is clearly evident.

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