Trial Design Strategies for Vascular-Targeted Therapy of Patients with Ovarian Cancer

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Many women with ovarian cancer present with advanced disease, and although most respond to treatment, the majority relapse and eventually die of the disease. Therapy targeted against angiogenesis is a new strategy being investigated in ovarian cancer. We review current trials directed against vascular endothelial growth factor (VEGF), the dominant proangiogenic vascular growth factor in ovarian cancer. Two main groups of inhibitors are being investigated in randomized trials. In the first group is bevacizumab, a monoclonal antibody (MoAb) that targets VEGF and is being evaluated in the first-line treatment of ovarian cancer. In the second group are VEGF receptor tyrosine kinase inhibitors (TK; TKIs). Cediranib (AZD2171) is one agent now being studied in a randomized trial (ICON6) in women with platinumsensitive first relapse. ICON6 is a 3-arm study investigating cediranib in combination with platinum-paclitaxel and as maintenance after chemotherapy. The trial design is novel with 3 sequential phases assessing toxicity, activity, and survival combined within a single randomized, placebo-controlled trial to improve the speed of evaluation of the new compound, saving costs and using patient data efficiently. VEGF inhibitors are more cytostatic than cytotoxic, and stable disease (SD) rather than overall response is often the best “response.” Novel trial designs to assess antiangiogenic agents are needed to unravel questions about dose and scheduling of the growing number of antiangiogenic agents in a rapid and efficient manner. International collaboration is essential as is a close partnership between academia and industry to make such trials feasible.

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