Anticancer effects of chemoembolization using microspheres of an angiogenesis inhibitor (TNP-470) in rabbits bearing VX-2 carcinoma

Abstract

Chemoembolization is a useful cancer treatment which combines chemotherapy and tumor devascularization using an anticancer drug and transcatheter embolization of the arteries running to the tumor. TNP-470 is a new type of anticancer durg which prevents tumor neovascularization thereby blocking nutrient supply. We expected that the chemoembolization using microspheres containing this angiogenesis inhibitor would produce strong anticancer activity attributed to sitespecific inhibition of the tumor neovascularization, especially the development of collateral circulation. We examined the anticancer effects of chemoembolization using TNP-470 microspheres prepared with poly(DL-lactic/glycolic acid) in rabbits bearing VX-2 carcinoma. It is assumed that microspheres of 53-125 μm in diameter persistently embolized the arterial capillaries surrounding the tumor for 2∼3weeks and released the drug over 5 days. When TNP-470 was injected s. c. 5 times at a dose of 5 mg at 2-or 3-day intervals, tumor growth was found to be significantly inhibited after the 3rd injection(P<0.05). A single i. a. injection of 1 mg of TNP-470 aqueous solution or 50 mg of placebo microspheres provided slight suppression of tumor growth, but microspheres containing the same dose of TNP-470 caused striking regression of the tumor for 9 days, and this effect was dose-dependent. Chemoembolization should offer promising and reliable therapy using angiogenesis inhibitors with less systemic side effects.