Antitumor effects of angiogenesis inhibitor TNP-470 in rabbits bearing VX-2 carcinoma by arterial administration of microspheres and oil solution.
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.
Kamei
S
S
DDS Research Laboratories, Takeda Chemical Industries, Ltd., Osaka, Japan.
Okada
H
H
Inoue
Y
Y
Yoshioka
T
T
Ogawa
Y
Y
Toguchi
H
H
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000494:pharmacology*; D002277:Carcinoma / Q000098:blood supply*; D003510:Cyclohexanes; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D007269:Injections, Intra-Arterial; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D007459:Iodized Oil / Q000008:administration & dosage; D008297:Male; D008863:Microspheres; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000098:blood supply* / Q000188:drug therapy; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D011817:Rabbits; D012717:Sesquiterpenes / Q000008:administration & dosage / Q000494:pharmacology*; D012996:Solutions
D000903:Antibiotics, Antineoplastic; D003510:Cyclohexanes; D012717:Sesquiterpenes; D012996:Solutions; D007459:Iodized Oil; D004317:Doxorubicin; D000077609:O-(Chloroacetylcarbamoyl)fumagillol