Enhanced antitumor effect of 5'-deoxy-5-fluorouridine by oral administration with L-cysteine

Abstract

When given orally in combination with L-cysteine, 5'-deoxy-5-fluorouridine (DFUR) brought about a significant reduction in the growth of adenocarcinoma 755 and a significant prolongation of life-span in mice bearing Lewis lung carcinoma without increased toxicity to the host as compared with DFUR alone, though L-cysteine alone did not show an appreciable antitumor activity. Moreover, the combination of DFUR and L-cysteine resulted in a marked retardation of growth of human colon tumor LS174T transplanted into nude mice. Thus, the potency of DFUR was increased by L-cysteine. Pharmacokinetic studies revealed that after DFUR administration, plasma DFUR and 5-fluorouracil (5-FU) levels rapidly declined, but that, in the combination with L-cysteine, the plasma clearances of DFUR and 5-FU were slowed down considerably. In the tumor, DFUR and 5-FU levels were similar to those in the plasma. Such a prolongation of DFUR and 5-FU levels in plasma and tumor may produce the enhancement of antitumor effect seen with the combination of DFUR and L-cysteine.