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

This study was conducted to evaluate the effectiveness of angiogenesis inhi bitor 6-O-(N-chloroacetyl-carbamoyl)-fumagillol (TNP-470, AGM-1470) in the treatment of nasopharyngeal carcinoma (NPC) alone and in combination with c ytotoxic agents. Forty-two male BALB/c nude mice bearing human NPC cell lin e 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 enha ncement in antitumor efficacy. TNP-470 also enhanced the inhibitory effect of DDP, although not to statistical significance. All animals gained in bod y weight, although treatment with 5-FU caused slight, reversible diarrhea o f 2 to 3 days' duration. The results showed that TNP-470 suppressed the gro wth of the human NPC cell line and enhanced the antitumor effect of 5-FU wi thout increasing its toxicity. The combination of angiogenesis inhibitors w ith conventional cytotoxic agents is promising in the treatment of NPC.