Combinations of 5-FU, hypoxanthine, and allopurinol in chemotherapy for human colon adenocarcinoma xenografts

A series of four human colon adenocarcinomas, growing as xenografts in immune-deprived mice, have been used to evaluate the efficacy of 5-FU in combination with two purines, hypoxanthine (Hx) and allopurinol (HPP), which have reduced the toxicity of 5-FU in host mice. Tumor-bearing mice were treated at 7-day intervals with 5-FU administered simultaneously with the protecting agents (Hx and HPP). Two tumor lines (HxVRC₅ and HxGC₃), insensitive to 5-FU alone, failed to show any response to this combination. In 5-FU-sensitive HxELC₂ tumors, the combination of 5-FU with Hx and HPP did not increase the therapeutic index, and in HxHC₁ xenografts, antagonism to 5-FU cytotoxicity was observed. Tumor response in relation to the pathways of 5-FU metabolism is discussed.