[Biochemical modulation applied to experimental cancer chemotherapy].
The biochemical modulation (BCM) of the antitumor effect of 5-fluorouracil (5-FU) by leucovorin (LV) was studied with xenografts (MC-1, MC-3, MPC-2) by transplanting human tumors to nude mice and by human tumor clonogenic assay (HTCA). For human tumor transplantation to nude mice, the dose of 5-FU was set at LD50 x 0.6 or LD50 x 0.8 and LV was given in three doses, 0.45, 0.15, 0.06 mg/body. Antitumor effects of combined administration of 5-FU and LV at the same time, as compared with that of administration of LV one hour before 5-FU, were examined. The relationship between the rate of inhibition of thymidylate synthetase (T.S) activity and 5-FU concentration in the neoplastic tissues was also examined. In HTCA the antitumor effects of 5-FU were examined by two methods: 1) limited contact for one four, and 2) continuous contact for two weeks. In the human tumor transplantation to nude mice, the BCM of the antitumor effect of 5-FU by LV was demonstrated in MC-1 and MPC-2. This BCM function of LV was enhanced by administering it one hour before 5-FU. The suitable LV dose was between 0.15 and 0.45 mg/body. Although there was a tendency for the rate of inhibition of T.S to be proportional to the tissue concentration of 5-FU, there was no significant relationship between the T.S inhibition rate and the antitumor effect. In HTCA, the BCM function of LV was suggested by the two-week-continuous contact method with MC-1 and MPC-2. Depending on the method of administering LV, the antitumor activity was higher with two-week continuous contact than with one-hour contact. In conclusion, the BCM effect of LV on the antitumor effect of 5-FU was revealed in MC-1 and MPC-2 strains. Further studies are needed to establish a standard for appropriate dosage and administration of LV.
Nakamura
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Y
Department of Otolaryngology, Teikyo University, School of Medicine, Tokyo.
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000493:pharmacokinetics; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage / Q000493:pharmacokinetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D014183:Transplantation, Heterologous
D002955:Leucovorin; D005472:Fluorouracil