Phase II Study of Bevacizumab in Patients With Platinum-Resistant Ovarian Cancer or Peritoneal Serous Cancer

American Society of Clinical Oncology (ASCO) - Tập 25 Số 33 - Trang 5180-5186 - 2007
Stephen A. Cannistra1, Ursula A. Matulonis1, Richard T. Penson1, Julie Hambleton1, Jakob Dupont1, Howard M. Mackey1, Jeffrey A. Douglas1, Robert A. Burger1, Deborah K. Armstrong1, Robert M. Wenham1, William P. McGuire1
1From the Beth Israel Deaconess Medical Center; Dana-Farber Cancer Institute; Massachusetts General Hospital, Boston, MA; Genentech Inc, South San Francisco; University of California at Irvine, Orange, CA; The Johns Hopkins Kimmel Cancer Center; Franklin Square Hospital, Baltimore, MD; and Moffitt Cancer Center, Tampa, FL

Tóm tắt

Purpose We evaluated the efficacy and safety of bevacizumab in patients with platinum-resistant epithelial ovarian carcinoma (EOC) or peritoneal serous carcinoma (PSC) who had experienced disease progression during, or within 3 months of discontinuing, topotecan or liposomal doxorubicin. Patients and Methods No more than three prior treatment regimens were allowed. Patients received single-agent bevacizumab 15 mg/kg intravenously every 3 weeks. Response was assessed by computed tomography (CT) scan every 6 weeks using Response Evaluation Criteria in Solid Tumors (RECIST). Results Of 44 patients treated, 83.7% were primarily platinum resistant, 59.1% had received liposomal doxorubicin, 25% topotecan, 15.9% both agents, and 47.7% had received three prior chemotherapy regimens. A median of five (range, two to 16) bevacizumab doses were administered. Partial responses were observed in seven patients (15.9%). Median progression-free survival was 4.4 months (95% CI, 3.1 to 5.5 months), with a median survival duration of 10.7 months at study termination. Bevacizumab-associated grade 3 to 4 events included hypertension (9.1%), proteinuria (15.9%), bleeding (2.3%), and wound-healing complications (2.3%). The incidence of GI perforation (GIP; 11.4%) was higher than reported in bevacizumab trials of other tumor types. GIP occurred in 23.8% of patients receiving three prior chemotherapy regimens, compared with 0% of patients receiving two prior chemotherapy regimens (P < .01). A trend toward higher risk of GIP was observed for patients with bowel wall thickening or bowel obstruction on CT scan. Arterial thromboembolic events occurred in three patients (6.8%). Three deaths were related to bevacizumab treatment. Conclusion Bevacizumab has single-agent activity in patients with platinum-resistant EOC or PSC. A higher than expected incidence of GIP was noted in these heavily pretreated patients.

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Tài liệu tham khảo

10.3322/canjclin.57.1.43

10.1056/NEJMra041842

10.1200/JCO.2002.20.5.1158

10.1200/JCO.2001.19.14.3312

10.1038/bjc.1997.537

Abu-Jawdeh GM, Faix JD, Niloff J, et al: Strong expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in ovarian borderline and malignant neoplasms. Lab Invest 74:1105,1996-1115,

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,

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,

10.1097/00004347-199707000-00011

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

10.1200/JCO.2001.19.3.843

Burger RA, Sill M, Monk B, et al: Phase II trial of bevacizumab in persistent or recurrent epithelial ovarian cancer (EOC) or primary peritoneal cancer: A Gynecologic Oncology Group (GOG) study. J Clin Oncol 23:457s,2005, (suppl; abstr 5009)

10.1200/JCO.2005.02.129

10.1093/jnci/92.3.205

10.1200/JCO.2001.19.20.4054

10.1016/S0167-9473(99)00015-8

10.1056/NEJMoa021491

10.1200/JCO.2005.08.955

10.1053/j.seminoncol.2003.08.013

10.1056/NEJMoa061884

10.3816/CBC.2003.n.007

10.1056/NEJMoa032691

AVASTIN package insert . South San Franciso, CA, Genentech Inc, 2005

10.1002/cncr.21969

10.1200/jco.2005.23.16_suppl.3020

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American Society of Clinical Oncology (ASCO)

Tập 25 Số 33

5180-5186

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