Combination of angiogenesis inhibitor TNP-470 with cytotoxic drugs in experimental therapy of nasopharyngeal carcinoma

Ann Otol Rhinol Laryngol. 2000 Jul;109(7):641-5. doi: 10.1177/000348940010900705.

Abstract

This study was conducted to evaluate the effectiveness of angiogenesis inhibitor 6-O-(N-chloroacetyl-carbamoyl)-fumagillol (TNP-470. AGM-1470) in the treatment of nasopharyngeal carcinoma (NPC) alone and in combination with cytotoxic agents. Forty-two male BALB/c nude mice bearing human NPC cell line CNE-2 were randomized into 6 groups: those treated with saline solution, TNP-470, cisplatin (DDP), fluorouracil (5-FU), TNP-470 + DDP, and TNP-470 + 5-FU, respectively. In every treatment group, tumor growth was suppressed significantly. The combination of 5-FU with TNP-470 showed significant enhancement in antitumor efficacy. TNP-470 also enhanced the inhibitory effect of DDP, although not to statistical significance. All animals gained in body weight, although treatment with 5-FU caused slight, reversible diarrhea of 2 to 3 days' duration. The results showed that TNP-470 suppressed the growth of the human NPC cell line and enhanced the antitumor effect of 5-FU without increasing its toxicity. The combination of angiogenesis inhibitors with conventional cytotoxic agents is promising in the treatment of NPC.

MeSH terms

  • Angiogenesis Inhibitors / administration & dosage*
  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Cisplatin / administration & dosage
  • Cyclohexanes
  • Drug Evaluation, Preclinical
  • Fluorouracil / administration & dosage
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Nasopharyngeal Neoplasms / drug therapy*
  • Nasopharyngeal Neoplasms / pathology
  • Neoplasm Transplantation
  • O-(Chloroacetylcarbamoyl)fumagillol
  • Sesquiterpenes / administration & dosage*
  • Tumor Cells, Cultured

Substances

  • Angiogenesis Inhibitors
  • Antineoplastic Agents
  • Cyclohexanes
  • Sesquiterpenes
  • Cisplatin
  • Fluorouracil
  • O-(Chloroacetylcarbamoyl)fumagillol