Incorporation of anti-angiogenesis therapy in the management of advanced ovarian carcinoma—Mechanistics, review of phase III randomized clinical trials, and regulatory implications

摘要: Despite survival gains achieved nearly two decades ago with combination platinum- and taxane-based intravenous chemotherapy, overall curves have remained relatively unchanged during the 21st century using newer cytotoxic agents. Although combined intravenous-intraperitoneal (IV-IP) chemotherapy is promising, tolerability remains a significant issue. An emphasis has been placed on exploring dose dense schedules targeted Vascular endothelial growth factor (VEGF) emerged as an important therapeutic target in several solid tumors including ovarian carcinoma. The monoclonal antibody, bevacizumab, binds VEGF, thus preventing activation of VEGF receptor (VEGFR) leading to inhibition tumor angiogenesis. To date eight phase 3 randomized controlled trials incorporating anti-angiogenesis therapy treatment newly diagnosed recurrent carcinoma met their primary endpoints. Four these included bevacizumab were reported from 2010 2012. During 2013, other four studies reported, each studying one following novel agents: pazopanib, cediranib, trebananib, nintedanib. Importantly, none drugs approved by United States Food Drug Administration (US FDA) for cancer. purpose this review will be highlight both VEGF-dependent non-VEGF dependent angiogenic pathways cancer discuss experiences regulatory implications targeting microenviroment therapy.