Importance of Bevacizumab Maintenance Following Combination Chemotherapy in Human Non-small Cell Lung Cancer Xenograft Models.
Bevacizumab in combination with chemotherapeutics has shown significant survival benefit in clinical studies in patients with non-small cell lung cancer (NSCLC). Since bevacizumab was administered as standard treatment until disease progression, the importance of bevacizumab during the maintenance phase was not prospectively investigated in these studies.



Three human NSCLC cell line xenograft models were used to investigate antitumor effect of bevacizumab and tumor microvessel density (MVD) was analyzed.



In A549 and NCI-H292 models, bevacizumab maintenance following combination with paclitaxel exhibited stronger tumor suppression than its absence. In an NCI-H292 model, bevacizumab maintenance continuously inhibited increase of MVD. In an NCI-H2228 model following induction treatment with pemetrexed and bevacizumab, maintenance with 
pemetrexed plus bevacizumab, had stronger efficacy than pemetrexed alone and led to lower MVD and level of thymidylate synthase.



Continuous suppression of angiogenesis by bevacizumab may contribute to the superior efficacy of maintenance treatment containing bevacizumab.
Product Research Department, Chugai Pharmaceutical Co., Ltd., Kamakura, Japan ishikuranby@chugai-pharm.co.jp.
Nobuyuki
N
Ishikura
Product Research Department, Chugai Pharmaceutical Co., Ltd., Kamakura, Japan.
Mieko
M
Yanagisawa
Product Research Department, Chugai Pharmaceutical Co., Ltd., Kamakura, Japan.
Mariko
M
Noguchi-Sasaki
Product Research Department, Chugai Pharmaceutical Co., Ltd., Kamakura, Japan.
Toshiki
T
Iwai
Product Research Department, Chugai Pharmaceutical Co., Ltd., Kamakura, Japan.
Keigo
K
Yorozu
Product Research Department, Chugai Pharmaceutical Co., Ltd., Kamakura, Japan.
Mitsue
M
Kurasawa
Product Research Department, Chugai Pharmaceutical Co., Ltd., Kamakura, Japan.
Masamichi
M
Sugimoto
Product Research Department, Chugai Pharmaceutical Co., Ltd., Kamakura, Japan.
Kaname
K
Yamamoto
D000072283:A549 Cells; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D000068258:Bevacizumab / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D006801:Humans; D060828:Induction Chemotherapy; D008175:Lung Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D060046:Maintenance Chemotherapy; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000473:pathology / Q000517:prevention & control*; D000068437:Pemetrexed / Q000008:administration & dosage; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
D000068437:Pemetrexed; D000068258:Bevacizumab
Bevacizumab; angiogenesis; maintenance therapy; non–small cell lung cancer; paclitaxel; pemetrexed; thymidylate synthase