Enhanced Antitumor Effect of 5′‐Deoxy‐5‐fluorouridine by Oral Administration with l‐Cysteine

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 antitnmor 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.