Prolongation of survival period and improvement of cancer cachexia by long-term administration of UFT.
We assayed the antitumoral and anticachectic activity of an oral fluoropyrimidine, UFT using the Colon-26-bearing murine cachexia model in terms of the survival period and parameters corresponding to clinical symptoms. Tumor growth was inhibited by UFT dose-dependently at the dose range of 12.5-25.0 mg/kg per day. Although UFT did not show significant growth inhibition at 15.0 and 12.5 mg/kg to which UFT gave little toxicity, the survival period was shown to be superior to the case of maximum tolerated dose (25.0 mg/kg per day). Next, we compared the maximum increase of life span (ILS) value for an administration schedule of continuous 9 days and 5 weeks which mimics the clinical schedule and found that the ILS value in the latter group was superior to the former and UFT improved cachexia, in the same manner. In the following experiments, we have clarified that UFT decreased the level of both plasma interleukin-6 (IL-6) and tumorous prostaglandin E2 (PGE2) and it highly accelerated IL-6 production from Colon-26. These findings suggest that UFT therapy, in low-toxic dose, could be useful to cachectic patients with poor performance status.
Nukatsuka
M
M
Anticancer & Antimicrobial Research Lab., Taiho Pharmaceutical Co., Ltd. Tokushima-Shi, Japan.
Fujioka
A
A
Saito
H
H
Uchida
J
J
Nakano
K
K
Takeda
S
S
Unemi
N
N
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols; D002100:Cachexia / Q000188:drug therapy*; D004285:Dogs; D004334:Drug Administration Schedule; D004338:Drug Combinations; D015850:Interleukin-6 / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000401:mortality; D005641:Tegafur / Q000627:therapeutic use*; D014498:Uracil / Q000627:therapeutic use*
D004338:Drug Combinations; D015850:Interleukin-6; C096910:UFT(R) drug; D005641:Tegafur; D014498:Uracil