Importance of Bevacizumab Maintenance Following Combination Chemotherapy in Human Non-small Cell Lung Cancer Xenograft Models

• Published in: Anticancer research Vol. 37; no. 2; pp. 623 - 630
• Main Authors: Ishikura, Nobuyuki, Yanagisawa, Mieko, Noguchi-Sasaki, Mariko, Iwai, Toshiki, Yorozu, Keigo, Kurasawa, Mitsue, Sugimoto, Masamichi, Yamamoto, Kaname
• Format: Journal Article
• Language: English
• Published: Greece 01.02.2017
• Subjects: A549 Cells; Animals; Antineoplastic Combined Chemotherapy Protocols - pharmacology; Bevacizumab - administration & dosage; Carcinoma, Non-Small-Cell Lung - blood supply; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - pathology; Cell Line, Tumor; Humans; Induction Chemotherapy; Lung Neoplasms - blood supply; Lung Neoplasms - drug therapy; Lung Neoplasms - pathology; Maintenance Chemotherapy; Male; Mice, Inbred BALB C; Mice, Nude; Neovascularization, Pathologic - pathology; Neovascularization, Pathologic - prevention & control; Pemetrexed - administration & dosage; Tumor Burden - drug effects; Xenograft Model Antitumor Assays; paclitaxel; pemetrexed; angiogenesis; non–small cell lung cancer; maintenance therapy; thymidylate synthase; Bevacizumab
• ISSN: 0250-7005; 1791-7530
• DOI: 10.21873/anticanres.11356

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.