Maintenance treatment with bevacizumab prolongs survival in an in vivo ovarian cancer model.
OBJECTIVE
Vascular endothelial growth factor (VEGF) plays a central role in tumor angiogenesis and is regarded as a promising therapeutic target. We hypothesized that treatment with bevacizumab, a humanized recombinant anti-VEGF monoclonal antibody, could enhance antitumor response to cisplatin and prolong survival in a murine ovarian cancer model.


METHODS
We conducted an MTS assay to examine the effect of bevacizumab on proliferation of the VEGF producing human ovarian cancer cell lines in vitro. Next, the antiangiogenic activity of bevacizumab was investigated by in vivo angiogenesis and wound healing assays. We then determined the toxicity and antitumor response of bevacizumab and cisplatin as single agents or in combination in xenograft models of ovarian cancer. Finally, using the same xenograft model, we examined the effect of these regimens, as well as bevacizumab maintenance therapy, on survival.


RESULTS
Bevacizumab had no effect on the proliferation of ovarian cancer cells in vitro but significantly inhibited angiogenesis and delayed wound healing in vivo. Bevacizumab inhibited i.p. tumor growth and ascites production in the nu/nu mouse xenograft model and enhanced the therapeutic efficacy of cisplatin. Combination therapy with bevacizumab and cisplatin for 3 weeks was associated with complete disappearance of all macroscopic evidence of disease. Moreover, maintenance treatment with bevacizumab after 3 weeks of induction combination therapy inhibited recurrence and significantly prolonged survival.


CONCLUSIONS
Bevacizumab has significant antitumor activity not only as a single agent or in combination with cisplatin but may also prolong survival when used as maintenance therapy after a complete response to cisplatin-based chemotherapy.
Mabuchi
Seiji
S
Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan. smabuchi@gyne.med.osaka-u.ac.jp
Terai
Yoshito
Y
Morishige
Kenichiro
K
Tanabe-Kimura
Akiko
A
Sasaki
Hiroshi
H
Kanemura
Masanori
M
Tsunetoh
Satoshi
S
Tanaka
Yoshimichi
Y
Sakata
Masahiro
M
Burger
Robert A
RA
Kimura
Tadashi
T
Ohmichi
Masahide
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D000068258:Bevacizumab; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D002945:Cisplatin