Comparative effects of paclitaxel and docetaxel on the metabolism and pharmacokinetics of epirubicin in breast cancer patients

Purpose: To investigate whether paclitaxel and docetaxel influence the phar macokinetics 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 pa tients received epirubicin alone 90 mg/m(2) by intravenous (IV) bolus; eigh t patients received the same dose of epirubicin followed immediately by pac litaxel 175 mg/m(2) in a 3-hour infusion; the other eight patients received epirubicin 90 mg/m(2) followed immediately by docetaxel 70 mg/m(2) in a I- hour infusion. Epirubicin and its metabolites, epirubicinol(EOL) and 7-deox ydoxorubicinone (7d-Aone), were identified by high-pressure liquid chromato graphy. Results: No pharmacokinetic interaction between the parent compound epirubi cin and taxanes was detected. Conversely, a significant effect on epirubici n metabolism by both paclitaxel and docetaxel was found. Epirubicin given w ith paclitaxel or docetaxel yielded areas under the plasma concentration-ti me curves (AUC) for 7d-Aone 1.7-fold and 1.9-fold higher (P < .05), respect ively, than epirubicin alone. The appearance of two polar metabolites sensi tive to glucuronidase was also significantly greater in both taxane groups. Quantitatively different metabolic rates and patterns for EOL were observe d in the paclitaxel and docetaxel combinations. The EOL AUC after paclitaxe l 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 pa rent compound epirubicin and paclitaxel or docetaxel, A different pattern o f interaction between these taxanes and epirubicin metabolism is clearly ev ident. (C) 1999 by American Society of Clinical Oncology.