GREATER ANTITUMOR EFFICACY OF PACLITAXEL ADMINISTERED BEFORE EPIRUBICIN IN A MOUSE MAMMARY-CARCINOMA

Combined treatment with paclitaxel and anthracyclines is increasingly being tested in clinical practice. Epirubicin is in general administer ed before paclitaxel. We have investigated, using a murine mammary ade nocarcinoma, whether the efficacy and toxicity of this combination is influenced by treatment sequence, different time intervals and dose in tensity. The tumor was transplanted into the right hind foot of C3D2F1 female mice. Paclitaxel was administered i.p. in doses ranging from 1 5 mg/kg to 75 mg/kg and epirubicin (i.p. or i.v.) in doses from 9 mg/k g to 30 mg/kg. The hepatic and peritoneal toxicity observed with epiru bicin administration increased in combined treatments (stronger with i .p. than i.v. epirubicin administrations) and was dose-dependent. When paclitaxel and epirubicin were administered simultaneously or paclita xel was given 24 h before epirubicin, the same tumor growth delays wer e obtained in all groups. A smaller effect was observed when paclitaxe l was administered 24 h after epirubicin. Increasing the epirubicin or paclitaxel dose led to higher tumor growth delays but also an increas ed toxicity. In conclusion, in this experimental model, the administra tion of 45 mg/kg paclitaxel before 15 mg/kg epirubicin was very effect ive and the increased toxicity can be limited by introducing an interv al of 24 h between drug administrations. These results should be consi dered when designing clinical trials.