Potentiation of the chemotherapeutic effect of 5-fluorouracil by combination with guanosine 5'-monophosphate.

The chemotherapeutic effect of the 5-fluorouracil (5-FU)-guanosine 5'-monophosphate (GMP) combination in various mouse tumor systems was compared with that of 5-FU monotherapy. Antitumor activity of 5-FU against L-1210 leukemia was potentiated without increasing its toxicity to the host when GMP at 30-100 mg/kg/day was injected simultaneously with 5-FU. Any time interval between the administrations of 5-FU and GMP diminished the increase in survival. Moreover, the combination of 5-FU and GMP at 100 mg/kg/day produced marked antitumor effects in the P-388 leukemia, ascites sarcoma 180, and Ehrlich ascites carcinoma systems. GMP also potentiated the antitumor activity of 5-FU in solid tumor systems (adenocarcinoma 755 and Lewis lung carcinoma) when given by intravenous injection, but not intraperitoneal injection. The therapeutic effect of 5-FU on various murine tumors was markedly potentiated by GMP at 100 mg/kg/day or less without increasing the toxicity to the host.