Phase II Trial of Bevacizumab in Persistent or Recurrent Epithelial Ovarian Cancer or Primary Peritoneal Cancer: A Gynecologic Oncology Group Study

American Society of Clinical Oncology (ASCO) - Tập 25 Số 33 - Trang 5165-5171 - 2007
Robert A. Burger1, Michael W. Sill1, Bradley J. Monk1, Benjamin E. Greer1, Joel I. Sorosky1
1From the University of California, Irvine, Orange, CA; GOG Statistical and Data Center, Roswell Park Cancer Institute; Department of Biostatistics, University at Buffalo, Buffalo, NY; University of Washington, Seattle, WA; and the University of Iowa, Iowa City, IA

Tóm tắt

Purpose Vascular endothelial growth factor (VEGF) seems to be a promoter of tumor progression for epithelial ovarian cancer (EOC) and primary peritoneal cancer (PPC). We conducted a phase II trial to assess the efficacy and tolerability of single-agent bevacizumab, an anti-VEGF monoclonal antibody. Patients and Methods Eligible patients had persistent or recurrent EOC/PPC after one to two prior cytotoxic regimens, measurable disease, and Gynecologic Oncology Group performance status of at least 2. Treatment consisted of bevacizumab 15 mg/kg intravenously every 21 days until disease progression or prohibitive toxicity. Primary end points were progression-free survival (PFS) at 6 months and clinical response. Results The study consisted of 62 eligible and assessable patients, median age 57 years, 41 (66.1%) having received two prior regimens and 36 (58.1%) considered platinum resistant. Grade 3 adverse events at least possibly related to bevacizumab were hematologic (1), GI (3), hypertension (6), thromboembolism (1), allergy (2), hepatic (1), pain (3), coagulation (1), constitutional (1), and dyspnea (1). Grade 4 adverse events included pulmonary embolus (1), vomiting and constipation (1), and proteinuria (1). Thirteen patients (21.0%) experienced clinical responses (two complete, 11 partial; median response duration, 10 months), and 25 (40.3%) survived progression free for at least 6 months. Median PFS and overall survival were 4.7 and 17 months, respectively. There was no significant association of prior platinum sensitivity, age, number of prior chemotherapeutic regimens, or performance status with the hazard of progression or death. Conclusion Bevacizumab seems to be well tolerated and active in the second- and third-line treatment of patients with EOC/PPC and merits phase III investigation.

Từ khóa


Tài liệu tham khảo

10.3322/canjclin.56.2.106

10.1093/jnci/90.6.447

10.1200/JCO.2002.10.088

10.1007/s001099900019

Alvarez AA, Krigman HR, Whitaker RS, et al: The prognostic significance of angiogenesis in epithelial ovarian carcinoma. Clin Cancer Res 5:587,1999-591,

10.1002/(SICI)1097-0215(19960621)69:3<205::AID-IJC10>3.0.CO;2-6

Hollingsworth HC, Kohn EC, Steinberg SM, et al: Tumor angiogenesis in advanced stage ovarian carcinoma. Am J Pathol 147:33,1995-41,

10.1002/(SICI)1097-0142(19970701)80:1<98::AID-CNCR13>3.0.CO;2-A

Byrne AT, Ross L, Holash J, et al: Vascular endothelial growth factor-trap decreases tumor burden, inhibits ascites, and causes dramatic vascular remodeling in an ovarian cancer model. Clin Cancer Res 9:5721,2003-5728,

Gorski DH, Beckett MA, Jaskowiak NT, et al: Blockage of the vascular endothelial growth factor stress response increases the antitumor effects of ionizing radiation. Cancer Res 59:3374,1999-3378,

10.1016/S0002-9440(10)64467-7

Lee CG, Heijn M, di Tomaso E, et al: Anti-vascular endothelial growth factor treatment augments tumor radiation response under normoxic or hypoxic conditions. Cancer Res 60:5565,2000-5570,

10.1161/01.CIR.89.1.511

10.1093/jnci/92.3.205

10.1002/(SICI)1097-0258(19981030)17:20<2301::AID-SIM927>3.0.CO;2-X

10.1016/j.ygyno.2004.05.056

10.1002/(SICI)1096-9896(199908)188:4<369::AID-PATH381>3.0.CO;2-X

10.1038/sj.onc.1208246

10.1016/S0090-4295(99)00156-9

Price DJ, Miralem T, Jiang S, et al: Role of vascular endothelial growth factor in the stimulation of cellular invasion and signaling of breast cancer cells. Cell Growth Differ 12:129,2001-135,

Bevacizumab IND Action Letter . Bethesda, MD, Investigational Drug Branch, US Department of Health & Human Services, Cancer Therapy Evaluation Program, National Cancer Institute, 2005

10.1200/JCO.2001.19.3.843

10.1200/JCO.2005.08.955

10.1056/NEJMoa032691

10.1200/jco.2005.23.16_suppl.2

10.3816/CBC.2003.n.007

10.1016/j.ygyno.2004.12.001

10.1016/j.ygyno.2006.05.018

10.1016/j.ygyno.2006.05.006

10.1002/cncr.21969

10.1016/j.ygyno.2006.03.048

10.1016/j.ygyno.2006.01.030

Thông tin
Thông tin xuất bản

American Society of Clinical Oncology (ASCO)

Tập 25 Số 33

5165-5171

Thông tin tác giả