RT Journal Article
SR Electronic
T1 Antitumor activity of irofulven against human ovarian cancer cell lines, human tumor colony-forming units, and xenografts
JF International Journal of Gynecologic Cancer
JO Int J Gynecol Cancer
FD BMJ Publishing Group Ltd
SP 824
OP 831
DO 10.1136/ijgc-00009577-200409000-00013
VO 14
IS 5
A1 E. S. Van Laar
A1 E. Izbicka
A1 S. Weitman
A1 L. Medina-Gundrum
A1 J. R. Macdonald
A1 S. J. Waters
YR 2004
UL http://ijgc.bmj.com/content/14/5/824.abstract
AB The objective of this study was to investigate the cytotoxic activity of irofulven (HMAF, MGI 114), a unique chemotherapeutic agent currently under clinical investigation, in various preclinical models of ovarian cancer. Antiproliferative effects of irofulven in ovarian cancer cell lines and ovarian tumor specimens were characterized in vitro using sulforhodamine B and human tumor colony-forming assays, respectively. Irofulven demonstrated marked activity against a panel of ovarian tumor cell lines, including IGROV1, OVCAR-3, OVCAR-4, OVCAR-5, OVCAR-8, and SK-OV-3, all of which exhibit various drug resistance mechanisms. In human tumor cloning assays, irofulven inhibited colony formation in surgically derived ovarian tumors at concentrations as low as 0.001 μg /ml and indicated superior activity in comparison with paclitaxel when tested against the same tumor specimens. The antitumor activity of irofulven compared to that of paclitaxel was also examined using the SK-OV-3 xenograft model. In mice bearing subcutaneously implanted SK-OV-3 tumors, treatment with paclitaxel failed to inhibit tumor growth; whereas mice treated with maximum tolerated doses of irofulven had a 25% partial shrinkage rate, and the remaining animals had a mean tumor growth inhibition of 82%. The potent activity of irofulven against ovarian tumors in vitro and in vivo supports the evaluation of its clinical activity in ovarian cancer.