CONTINUOUS-INFUSION OF 5-FLUOROURACIL PLUS LOW-DOSE CISPLATIN IN TUMOR-BEARING MICE

Combination chemotherapy with 5-fluorouracil (5-FU) and cisplatin is w idely used but the optimal daily dose of the latter has not been estab lished. The present study was designed to determine the pharmacodynami c interaction and antitumor effect of these drugs when used at clinica lly relevant doses in animals. Male ddY mice were injected with Sarcom a 180 cells and then given a continuous infusion of 5-FU (10 mg/kg/day ) for 5 days (via an implanted micropump) +/- cisplatin 2 mg/kg by i.p . bolus (pharmacodynamic study), alternatively, mice were given 5-FU /- cisplatin (0.2 mg/kg/day), cisplatin alone for 5 days or no treatme nt (anti-tumor effect study). Tissue and serum samples were taken for analysis. No significant differences in serum pharmocokinetics were ob served between the groups at any timepoint but 0.5 h after the start o f infusion, where the serum 5-FU concentration was lower with monother apy than with combination therapy. 5-FU alone had a slight antitumor e ffect, while low dose cisplatin alone had no noticeable effect. 5-FU cisplatin produced a favorable response, with a significantly lower t reated/control tumor weight patio than in the non-treated and cisplati n monotherapy groups (p < 0.05), although this was not significantly d ifferent from the response to 5-FU monotherapy. In conclusion, the dos e of cisplatin used in the present study was insufficient to generate a significant tumor response alone but it did fend to enhance the anti tumor efficacy of 5-FU. Continuous 5-FU infusion plus low-dose daily c isplatin may become clinically useful after further investigation.