Ovarian tumor growth regression using a combination of vascular targeting agents anginex or topomimetic 0118 and the chemotherapeutic irofulven.
Combination of chemotherapeutic agents and angiogenesis inhibitors is now commonly employed in the clinic to treat cancer. Here, we used angiostatic agents anginex and 0118, in combination with the chemotherapeutic irofulven, to treat human ovarian tumor xenografts in mice. General linear mixed models were used to statistically analyze tumor growth curves. Overall, combination of a low, non-toxic dose of irofulven with either angiogenesis inhibitor was more effective at inhibiting tumor growth than any of the single agent therapies. For example, the anginex/irofulven and 0118/irofulven combinations inhibited tumor growth relative to controls by 92% (p<0.0001) and 96% (p<0.0001), respectively, with the 0118/irofulven combinations yielding 100% complete responses. This study suggests that combination therapy of 0118 or anginex and irofulven may be highly effective in the clinical setting.
Dings
Ruud P M
RP
Department of Biochemistry, Molecular Biology & Biophysics, University of Minnesota, Minneapolis, MN 55455, USA.
Van Laar
Emily S
ES
Webber
Jeremy
J
Zhang
Yan
Y
Griffin
Robert J
RJ
Waters
Stephen J
SJ
MacDonald
John R
JR
Mayo
Kevin H
KH
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D047250:Calixarenes / Q000627:therapeutic use; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006801:Humans; D051379:Mice; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D010455:Peptides; D011506:Proteins / Q000627:therapeutic use*; D012717:Sesquiterpenes / Q000627:therapeutic use*; D023041:Xenograft Model Antitumor Assays
D020533:Angiogenesis Inhibitors; D010455:Peptides; D011506:Proteins; D012717:Sesquiterpenes; C111993:betapep-25 protein, synthetic; C530377:compound 0118; D047250:Calixarenes; C102714:irofulven