Chemotherapeutic efficacy of 5-fluorouracil with concurrent thymidine infusion against transplantable colon tumors in rodents.

The therapeutic efficacy of 5-fluorouracil (FU) given concomitantly with thymidine (TdR) versus that of FU alone at an equitoxic dose was evaluated when these agents were given by 72-h continuous i.v. infusion or as an i.v. push dose through the tail vein to Fischer rats bearing a transplantable colon carcinoma or to BALB/c or C57BL/6J mice bearing murine colon tumors no. 26 or 38, respectively. In the presence of TdR, the dose of FU maximally tolerated by normal rats and mice was reduced by approximately half. In tumor-bearing rats, infusion of FU alone (150 mg/kg X 72 h) was as effective as concurrent infusion of FU (100 mg/kg X 72 h) with TdR (5 g/kg X 72 h), as evaluated in terms of tumor-free survivors (7/22 and 6/20, respectively). In addition, both regimens were more effective than an i.v. push dose of FU (200 mg/kg) or FU (80 mg/kg) and TdR (2 g/kg), which resulted in 2/18 and 0/18 tumor-free survivors, respectively. No significant differences in tumor growth inhibition were seen using either murine colon tumor, whether FU or the FU with TdR combination was administered as an i.v. push dose or as an infusion. Quantitation of the levels of TdR and thymine (T) in rat plasma obtained during infusion of various doses of TdR showed dose-dependent levels of TdR and T, indicating conversion of TdR to T in vivo. These data showed that, under the conditions employed, TdR did not modify significantly the antitumor activity of FU against rodent colon tumors. The toxicity of FU, however, could be enhanced by the coadministration of TdR, probably due, in part, to a reduced degradation of FU resulting from competition by T.