UFT inhibits lung metastases in spontaneous metastasis model of lung cancer.
BACKGROUND
UFT, an oral 5-fluorouracil derivative, is the only drug that is effective as a postoperative adjuvant therapy for non-small cell lung cancer (NSCLC) [ ], but the mechanism of the action remains unclear. We examined whether UFT and/or its metabolite, gamma-hydroxybutyric acid (GHB) inhibits lung metastases in a mouse model.


METHODS
Lewis lung carcinoma cells were implanted into the foot pads of C57 BL/6 mice, and mice were treated with UFT or GHB.


RESULTS
Both the mean number of metastatic nodules and the mean lung weight for UFT-treated mice (11.4 and 192.1 mg, respectively) were significantly lower than those for saline-treated mice (41.5 and 415.0 mg, respectively) (p < 0.001 for both). UFT did not inhibit tumor growth at the primary sites (foot pads). No significant body weight loss was documented in UFT-treated mice. GHB did not inhibit development of lung metastases even when a higher dose was used.


CONCLUSIONS
UFT inhibits development of lung metastases without any toxicity in mouse model, which may explain the efficacy of postoperative administration of UFT for resected NSCLC.
Miyahara
R
R
Department of Thoracic Surgery, Kyoto University, Sakyo-ku, Kyoto, Japan.
Nakagawa
T
T
Ishikawa
S
S
Fukushima
M
M
Wada
H
H
Tanaka
F
F
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018827:Carcinoma, Lewis Lung / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000556:secondary; D004338:Drug Combinations; D006801:Humans; D006885:Hydroxybutyrates / Q000627:therapeutic use; D008175:Lung Neoplasms / Q000517:prevention & control / Q000556:secondary*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D005641:Tegafur / Q000627:therapeutic use*; D014498:Uracil / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D004338:Drug Combinations; D006885:Hydroxybutyrates; C096910:UFT(R) drug; D005641:Tegafur; C111420:4-hydroxybutyric acid; D014498:Uracil