Cisplatin plus paclitaxel and maintenance of bevacizumab on tumour progression, dissemination, and survival of ovarian carcinoma xenograft models.
BACKGROUND
Bevacizumab is being incorporated as first-line therapy with standard-of-care chemotherapy on epithelial ovarian carcinoma (EOC). We investigated bevacizumab combined with chemotherapy on tumour progression and mouse survival in EOC xenograft models.


METHODS
Bevacizumab was administered concomitantly with cisplatin plus paclitaxel (DDP+PTX), continued after induction (maintenance) or started after chemotherapy. The effect on tumour progression was monitored by bioluminescence imaging (BLI) (1A9-luc xenograft). Tumour dissemination into the peritoneal organs and ascites formation (HOC22 xenograft) was evaluated by histological analysis at the end of treatment (interim) and at euthanasia (survival). The effects on overall survival (OS) were investigated in both EOC models.


RESULTS
Bevacizumab with PTX+DDP delayed tumour progression in mice bearing EOC xenografts. OS was significantly extended, with complete responses, by bevacizumab continued after stopping chemotherapy in the HOC22 xenograft. Bevacizumab alone inhibited ascites formation, with only limited effect on tumour burden, but combined with PTX+DDP reduced ascites and metastases. Bevacizumab started after induction with PTX+DDP and maintained was equally effective on tumour progression and survival on 1A9-luc xenograft.


CONCLUSIONS
Bevacizumab combined with chemotherapy not only affected tumour progression, but when administered as maintenance regimen significantly prolonged survival, reducing ascites, and tumour dissemination. We believe our findings are consistent with the clinical results and shed light on the potential effects of this kind of treatment on tumour progression.
Department of Oncology, Mario Negri Institute for Pharmacological Research, 20156 Milan, Italy.
P
P
Oliva
A
A
Decio
V
V
Castiglioni
A
A
Bassi
E
E
Pesenti
M
M
Cesca
E
E
Scanziani
D
D
Belotti
R
R
Giavazzi
D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D000068258:Bevacizumab; D002277:Carcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000077216:Carcinoma, Ovarian Epithelial; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000008:administration & dosage; D018450:Disease Progression; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D061067:Antibodies, Monoclonal, Humanized; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D017239:Paclitaxel; D002945:Cisplatin