In vivo intratumor angiogenic treatment effects during taxane-based neoadjuvant chemotherapy of ovarian cancer

Background: The aim of our study was to analyze the effect of taxane-based chemotherapy on tumor angiogenesis in patients with advanced epithelial ovarian cancer. Methods: Within a prospective phase II trial, 32 patients with stage IIIC and IV ovarian cancer were treated with either two or three cycles of neoadjuvant chemotherapy prior to cytoreductive surgery. Carboplatin (AUC5) and docetaxel (75 mg/m(2)) were administered intravenously in a 3-weekly schedule. Changes in intratumor microvessel density (MVD) were assessed with immunohistochemistry by staining pre- and posttreatment surgical tumor specimens with panendothelial, neovascular and lymphatic vessel markers. Results: Mean values of MVD defined by CD31, CD34, CD105 and D2-40 antibodies showed 12.3, 21.0, 2.7 and 3.1 vessels per high power field (HPF) before chemotherapy and increased after treatment to 15.3, 21.8, 4.8 and 3.6 per HPF, respectively. These changes were significant for CD31 (p = 0.04) and for CD105 (p = 0.02). Conclusion: Taxane-based chemotherapy appears to promote tumor vascularization when administered every 3 weeks. A possible explanation is the secondary recovery of MVD in response to immediate cytotoxic and antiangiogenic effects of the chemotherapy. If confirmed prospectively, these findings favor shorter treatment intervals of taxane-based chemotherapy to counteract proangiogenic recovery.