anti-VEGF monoclonal antibody bevacizumab for the treatment of recurrent uterine neoplasms. Patients and Methods: A retrospective analysis of women with recurrent uterine neoplasms

Background: Angiogenesis plays an important role in endometrial carcinogenesis. We reviewed our experience with the anti-VEGF monoclonal antibody bevacizumab for the treatment of recurrent uterine neoplasms. Patients and Methods: A retrospective analysis of women with recurrent uterine neoplasms treated with bevacizumab was performed. Results: A total of 11 patients were identified, 9 with epithelial endometrial carcinomas and 2 with leiomyosarcomas. All patients had multi-site disease and were heavily pretreated with a median of 3 prior chemotherapy regimens. All received bevacizumab combination therapy which was well-tolerated. Two patients had partial responses, 3 had stable disease, while 5 patients progressed. One subject was not assessable for response. The median progression-free interval was 5.4 months for the entire cohort and 8.7 months for those who achieved clinical benefit (PR or SD). Conclusion: Bevacizumab was welltolerated and displayed promising anti-neoplastic activity in patients with endometrial cancer and uterine leiomyosarcoma. Endometrial cancer is the most common gynecologic malignancy with nearly 41,200 cases expected in 2006 (1). Prognosis for patients with early stage disease confined to the uterus is excellent. However, the outcome for patients with recurrent, metastatic disease remains poor (2, 3). In a series of 379 patients with recurrent endometrial cancer the survival for women with pelvic recurrences was 12%. For patients with distant metastatic disease survival dropped to 5%, while only 2% of those with combined pelvic and distant failure were salvaged (2). Thus there is a clear need for agents with activity in the setting of recurrent disease. Angiogenesis plays an important role in the development and progression of endometrial cancer (4-7). Abulafia et al. noted a progressive increase in microvessel density (MVD) with the progression from benign endometrium to hyperplasia to invasive cancer (8). Increased vascular density is also associated with a poor prognosis. The 5-year overall survival was 82% in a cohort of endometrial cancer patients with low microvessel density compared to only 52% for those with high MVD (5). Additionally, high VEGF expression and microvessel density are associated with lymphvascular space invasion, nodal metastases and advanced stage disease (6). Angiogenesis therefore appears to be a potential therapeutic target for women with uterine neoplasms. Treatment with the monoclonal anti-VEGF antibody bevacizumab has demonstrated impressive results for a number of solid tumors (9, 10). Based upon these findings we have incorporated bevacizumab into the treatment of women with recurrent epithelial and mesenchymal uterine neoplasms. We describe the results of bevacizumab therapy for these patients, to our knowledge the first report of bevacizumab for uterine cancer. Patients and Methods Study approval was obtained from the Washington University Human Studies Committee. A review of institutional databases was then performed to identify patients with recurrent uterine tumors treated with the monoclonal, anti-vascular endothelial growth factor antibody bevacizumab between January 2005 and August 2006. Women with epithelial as well as mesenchymal lesions were included in the analysis. Patients treated with single agent bevacizumab as well as those treated with bevacizumab in combination with cytotoxic chemotherapy were examined. Toxicity was assessed and documented according the National Cancer Institute’s Common Toxicity Criteria version 3.0 guidelines. Response was determined based on radiographic evaluation. Response Criteria in Solid Tumors (RECIST) were utilized to 3525 Correspondence to: Jason D. Wright, MD, Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Columbia University College of Physicians and Surgeons, 161 Fort Washington Ave, 8th Floor, New York, NY 10032, U.S.A. Tel: +1 212 305 3410, Fax: +1 212 305 3412, e-mail: [email protected]