A Possible Clinical Adaptation of CRM197 in Combination with Conventional Chemotherapeutic Agents for Ovarian Cancer

作者：Tsujioka Hiroshi^*; Fukami Tatsuya; Yotsumoto Fusanori; Ueda Taeko; Hikita Shoko; Takahashi Yoko; Kondo Haruhiko; Kuroki Masahide; Miyamoto Shingo

来源：Anticancer Research, 2011, 31(7): 2461-2465.

• Ovarian cancer
• HB-EGF
• targeted therapy
• CRM197

Aim: Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a promising target for cancer therapy. We have already started a phase 1 study of CRM197, a specific HB-EGF inhibitor, for advanced ovarian cancer. In this study, we evaluated possible clinical adaptations of CRM197 in combination with conventional chemotherapeutic agents. Materials and Methods: CRM197, bevacizumab, and paclitaxel were intraperitoneally administered either alone or in combination with mice xenografted with ES2 human ovarian cancer cells. The tumor volumes and microvessel densities (MVD) were determined. Results: Enhanced antitumor effects were observed when paclitaxel was used in combination with bevacizumab or CRM197. The antitumor effect of paclitaxel/CRM197 was significantly higher than that of paclitaxel/bevacizumab. The tumor MVD of mice treated with paclitaxel/CRM197 was significantly lower than that of mice treated with paclitaxel/bevacizumab. Conclusion: CRM197 in combination with paclitaxel significantly blocked tumor formation and angiogenesis. These results suggest that paclitaxel is a suitable candidate for CRM197 combination therapy.

• 出版日期2011-7