Influence of molar ratio on the combination effect of 5-fluorouracil with guanosine 5'-monophosphate on P388 and L1210 leukemias.

To obtain more effective treatment with the combination of 5-fluorouracil (FUra) and guanosine 5'-monophosphate (GMP), the influence of the time interval between FUra and GMP administration and of the molar ratio of GMP to FUra on the effect on P388 murine leukemia were investigated. The antitumor activity of FUra was significantly potentiated when GMP was administered either 0-60 min before or 5 min after FUra. The potentiated increase in lifespan (ILS) was almost the same as after simultaneous injection of the two agents. Coadministration of FUra and GMP increased the antitumor activity as compared with the respective dose of FUra alone in a treatment schedule of either day 1 only or days 1-9. The multiple-dose regimen (days 1-9) was more effective than a single high-dose regimen, and a GMP/FUra molar ratio of 4 seems to achieve the best therapeutic results against P388 leukemia. Daily simultaneous administration of FUra and GMP on days 1-9 also resulted in a significant increase in the antitumor activity against L1210 Leukemia as compared with FUra alone.