Fixed-dose-rate administration of gemcitabine in cancer-bearing cats: A pilot study

Gemcitabine is an antimetabolite chemotherapy agent with schedule-dependent metabolism and efficacy. The purpose of this study was to identify the fixed-dose-rate (FDR) of gemcitabine administration in cancer-bearing cats that achieved a target plasma concentration (TPC) of 10 to 20 μM. Fifteen client-owned cats received gemcitabine infusions administered at various FDR for 1 to 6 hours. Plasma gemcitabine and dFdU (2',2'-difluorodeoxyuridine), the major gemcitabine metabolite, were quantitated by high performance liquid chromatography. Cats treated with an FDR less than 2.5 mg/m² per minute failed to achieve TPC, whereas cats treated with an FDR of 10 mg/m² per minute quickly exceeded the target range. An FDR of 5 mg/m² per minute provided the longest duration of exposure without exceeding the upper limit of the TPC. Plasma dFdU concentration mirrored plasma gemcitabine concentrations. These data suggest that in order to maintain TPC of gemcitabine in cats the FDR lies between 2.5 and 5 mg/m² per minute. A Phase II study to evaluate efficacy and toxicity of this approach is underway.