Abstract
The antitumor activities of an angiogenesis inhibitor, (3R,4S,5S,6R)-5- methoxy-4-[(2R,3R)-2-methyl-3-(3-methyl-2-butenyl)-oxiranyl]-1- oxaspiro[2,5]oct-6-yl(chloroacetyl) carbamate (TNP-470), administered s.c., i.v. and intra-arterially using a chemoembolization technique, were examined in rabbits bearing VX-2 carcinoma. Repeated s.c. injection of TNP-470 aqueous solution clearly inhibited the tumor growth in proportion to the dose, and improved efficacy was obtained with once a week s.c. administration of microspheres, which provide sustained release of TNP-470. Moreover, the injection of the TNP-470 microspheres into the predominant artery of the tumor via a catheter, chemoembolization, resulted in dramatic regression of the tumor. This antitumor effect was enhanced by coadministration of doxorubicin hydrochloride aqueous solution. Arterial administration of TNP-470 oil solution provided more persistent tumor growth inhibition due to the prolonged release and targeting of the angiogenesis inhibitor to the tumor.
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Antitumor effects of angiogenesis inhibitor TNP-470 in rabbits bearing VX-2 carcinoma by arterial administration of microspheres and oil solution.
