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

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/m2) 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.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).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.Although about 80% of advanced ovarian cancer patients respond well to standard management - primary cytoreductive surgery followed by platinum/taxane-based chemotherapy - the majority of patients develop recurrent disease and die of progressive disease[1]. Therefore changes in therapeutic procedures are of clinical interest.The application of neoadjuvant chemotherapy in advanced ovarian cancer is the subject of past and recent study efforts [2-4]. Results of a recently reported phase 3 study with 704 patients enrolled and a treatment schedule with 3 cycles carboplatin/paclitaxel preoperatively demonstrated that neoadjuvant chemotherapy produces similar PFS and OS rates compared to standard primary cytoreductive surgery and provides a significantly lower perioperative morbidity and mortality in