UFT inhibits lung metastases in spontaneous metastasis model of lung cancer

Thorac Cardiovasc Surg. 2005 Apr;53(2):118-21. doi: 10.1055/s-2004-830361.

Abstract

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.

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Carcinoma, Lewis Lung / pathology
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / secondary
  • Drug Combinations
  • Humans
  • Hydroxybutyrates / therapeutic use
  • Lung Neoplasms / prevention & control
  • Lung Neoplasms / secondary*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neoplasm Transplantation
  • Tegafur / therapeutic use*
  • Uracil / therapeutic use*

Substances

  • Antineoplastic Agents
  • Drug Combinations
  • Hydroxybutyrates
  • UFT(R) drug
  • Tegafur
  • 4-hydroxybutyric acid
  • Uracil