[Effect and mechanism of orally administered leucovorin/5-fluorouracil on colon cancer].
Leucovorin (LV)/5-fluorouracil combination is one of the first-line forms of chemotherapy for colorectal cancer, and in this regimen it was recommended that 5-FU be infused continuously from the venous route. However, since this regimen limits the patients' ADL, oral administration is preferable. The purpose of this study is to elucidate the mechanisms of orally-administered LV/5-FU.


METHODS
The Gastrostomy was performed, and 1 x 10(6) of colon 26 was transplanted subcutaneously in CDF1 mice. In the continuous administration group, either 10, 20, 40 mg/kg of 5-FU and 100 mg/kg of LV were continuously infused for 7 days following gastrostomy using a microinfusion pump (n = 6). In the single infusion group, either 10, 20, 40 mg/kg of 5-FU was infused once a day for 7 days after gastrostomy concomitant with LV (n = 6). The other 6 animals served as the control, and LV alone was infused in this group. Tumor volume, thymidylate synthase inhibition rate (TSIR), incorporation of 5-FU into RNA (F-RNA) and body weight were measured at the end of the treatment. During the experimental period, mice were given free access to chow and water.


RESULTS
The tumor volume suppression rate was significantly higher along with the amount of 5-FU. However, there was no significant difference between continuous and single infusion groups. TSIR was higher in the continuous group at the dose of 20 and 40 mg/kg. In contrast, F-RNA was higher in the single group at the dose of 20 and 40 mg/kg. Significant body weight loss was not recognized in any group.


CONCLUSIONS
From these data, single administration of 5-FU is more effective for RNA dysfunction. On the other hand, continuous infusion is more damaging to DNA duplication. In summary, since the mechanism of the antitumor effect differs with the administration method, it is important to understand this mechanism.
Iba
Toshiaki
T
Dept. of Surgery, Juntendo University Urayasu Hospital.
Kidokoro
Akio
A
Fukunaga
Masaki
M
Sugiyama
Kazuyoshi
K
Fukunaga
Tetsu
T
Aihara
Nobuyoshi
N
D000284:Administration, Oral; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D001835:Body Weight / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D004334:Drug Administration Schedule; D005472:Fluorouracil / Q000008:administration & dosage; D002955:Leucovorin / Q000008:administration & dosage; D051379:Mice; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors
D013940:Thymidylate Synthase; D002955:Leucovorin; D005472:Fluorouracil