BROMODEOXYURIDINE IMPROVES THE CYTOTOXIC EFFECT OF CISPLATIN - A COMPARISON WITH 5-FLUOROURACIL

We compared the effects of the radiosensitizers, 5-bromo-2'-deoxyuridi ne (BUdR) and 5-fluorouracil (5-FU) alone and in combination and cis-d iamminedichloroplatinum (cisplatin, DDP) on the growth of B16 amelanot ic melanoma (B16a) tumors in mice. In a preliminary study, tumor growt h was significantly inhibited in the presence of BUdR and was further reduced with the combination of BudR and DDP. In a second experiment, BUdR was found to be more effective than 5-FU when used in combination with DDP. At the completion of the study, tumor volumes as a percenta ge of control values in mice treated with a single drug were as follow s: 5-FU (50 mg/kg per day for 7 days) 76.5% (P < 0.05), BUdR (100 mg/k g per day for 7 days) 68% (P < 0.05) and DDP (5 mg/kg x 3) 54% (P < 0. 01). Combining 5-FU and DDP at these dosages reduced volumes to 38% (P < 0.01), while BUdR + DDP-treated mice had tumor volumes only 28% (P < 0.001) the size of untreated controls. Furthermore, the toxicity, as demonstrated by a decrease in body weight and an increase in mortalit y, was more severe in mice receiving 5-FU than in those receiving in B UdR. DDP interacts synergistically with either BUdR or 5-FU in iis cyt otoxic action in vivo. No such relationship could be demonstrated in v itro, suggesting that the pharmacologic activity of these drugs may be responsible for the antitumor activity rather than direct cytotoxic e ffects. We propose that BUdR is more effective than 5-FU as a potentia tor of DDP in this murine melanoma model.