Sustained effect of continuous treatment with bevacizumab following bevacizumab in combination with chemotherapy in a human ovarian clear cell carcinoma xenograft model

Ishikura,Nobuyuki; Yorozu,Keigo; Kurasawa,Mitsue; Yanagisawa,Mieko; Sugimoto,Masamichi; Yamamoto,Kaname

doi:10.3892/or.2019.7211

Sustained effect of continuous treatment with bevacizumab following bevacizumab in combination with chemotherapy in a human ovarian clear cell carcinoma xenograft model

Authors:
- Nobuyuki Ishikura
- Keigo Yorozu
- Mitsue Kurasawa
- Mieko Yanagisawa
- Masamichi Sugimoto
- Kaname Yamamoto
View Affiliations

Affiliations: Product Research Department, Chugai Pharmaceutical Co., Ltd., Kamakura 247-8530, Japan
Published online on: June 26, 2019 https://doi.org/10.3892/or.2019.7211
Pages: 1057-1065
Copyright: © Ishikura et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Although bevacizumab maintenance following bevacizumab in combination with chemotherapy has demonstrated significant prolongation of progression-free survival in clinical studies in patients with ovarian cancer, the majority of the cancer cases in the study were of the serous histotype; therefore, data regarding clear cell carcinoma is limited. Furthermore, the efficacy of bevacizumab beyond progression has not yet been demonstrated in ovarian cancer. A xenograft model using the human ovarian clear cell carcinoma cell line RMG-I was used to investigate the antitumor effects and the mechanisms of bevacizumab in maintenance treatment and bevacizumab when administered beyond disease progression. In the RMG-I model, bevacizumab maintenance following bevacizumab in combination with paclitaxel exhibited increased tumor suppression, compared with its absence, and inhibited the increase of microvessel density (MVD) in tumors. Following disease progression during bevacizumab maintenance, continued bevacizumab treatment in combination with PEGylated liposomal doxorubicin as a secondary chemotherapeutic agent had increased efficacy, compared with PEGylated liposomal doxorubicin alone, and resulted in lower MVD accompanied with lower levels of insulin-like growth factor binding protein-3, which is reported to have angiogenic activity. Continuous suppression of angiogenesis by bevacizumab may contribute to the superior efficacy of bevacizumab maintenance and bevacizumab beyond progression in ovarian cancer.

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