Relationship between antitumor effect and metabolites of 5-fluorouracil in combination treatment with 5-fluorouracil and guanosine in ascites sarcoma 180 tumor system.

The antitumor activity of 5-fluorouracil (FUra) against ascites Sarcoma 180 was significantly enhanced by coadministration of guanosine, and slightly by adenosine, but not by cytidine or uridine. In advanced ascites Sarcoma 180, guanosine also enhanced the action of FUra, but adenosine, uridine, and cytidine did not. The potentiation of antitumor activity by guanosine was reversed by addition of cytidine.

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.

Effect of pyrimidines, purines and their nucleosides on antitumor activity of 5-fluorouracil against L-1210 leukemia.

The chemotherapeutic action of 5-fluorouracil (5-FU) monotherapy on L-1210 leukemia in mice was compared with combinations of pyrimidines (uracil, uridine, deoxyuridine, cytosine, cytidine, deoxycytidine, thymine and thymidine) or purines (adenine, adenosine, deoxyadenosine, guanine, guanosine, deoxyguanosine and inosine) with 5-FU. The antitumor activity of 5-FU was enhanced by coadministration of uracil, thymine or guanosine, but the toxicity of the first two compounds was also enhanced. Only when 5-FU was administered with guanosine, was not only the antitumor activity but also the therapeutic ratio potentiated without increasing its toxicity.

Antitumor activity of 1-acyloxymethyl derivatives of 5-fluorouracil against L1210 leukemia.

Antitumor activity of 15 1-acyloxymethyl derivatives of 5-fluorouracil was examined by both intraperitoneal injection and oral administration in L1210 leukemia system. Therapeutic ratio for dodecanoyloxymethyl derivative by intraperitoneal injection was 23 which was greater than that for 5-fluorouracil (11). On the other hand, undecanoyloxymethyl derivative of 5-fluorouracil showed the highest therapeutic ratio (5.