Bevacizumab Plus Irinotecan in Recurrent Glioblastoma Multiforme

American Society of Clinical Oncology (ASCO) - Tập 25 Số 30 - Trang 4722-4729 - 2007
James J. Vredenburgh1, Annick Desjardins1, James E. Herndon1, Jennifer Marcello1, David A. Reardon1, Jennifer A. Quinn1, Jeremy N. Rich1, Sith Sathornsumetee1, Sridharan Gururangan1, John H. Sampson1, Melissa Wagner1, Leighann Bailey1, Darell D. Bigner1, Allan H. Friedman1, Henry S. Friedman1
1From the Preston Robert Tisch Brain Tumor Center; and the Departments of Surgery, Medicine, Biostatistics, Pediatrics, Neurobiology, and Pathology, Duke University Medical Center, Durham, NC

Tóm tắt

Purpose The prognosis for patients with recurrent glioblastoma multiforme is poor, with a median survival of 3 to 6 months. We performed a phase II trial of bevacizumab, a monoclonal antibody to vascular endothelial growth factor, in combination with irinotecan. Patients and Methods This phase II trial included two cohorts of patients. The initial cohort, comprising 23 patients, received bevacizumab at 10 mg/kg plus irinotecan every 2 weeks. The dose of irinotecan was based on the patient's anticonvulsant: Patients taking enzyme-inducing antiepileptic drugs (EIAEDs) received 340 mg/m2, and patients not taking EIAEDs received 125 mg/m2. After this regimen was deemed safe and effective, the irinotecan schedule was changed to an accepted brain tumor regimen of four doses in 6 weeks, in anticipation of a phase III randomized trial of irinotecan versus irinotecan and bevacizumab. The second cohort, comprising 12 patients, received bevacizumab 15 mg/kg every 21 days and irinotecan on days 1, 8, 22, and 29. Each cycle was 6 weeks long and concluded with patient evaluations, including magnetic resonance imaging. Results The 6-month progression-free survival among all 35 patients was 46% (95% CI, 32% to 66%). The 6-month overall survival was 77% (95% CI, 64% to 92%). Twenty of the 35 patients (57%; 95% CI, 39% to 74%) had at least a partial response. One patient developed a CNS hemorrhage, which occurred in his 10th cycle. Four patients developed thromboembolic complications (deep venous thrombosis and/or pulmonary emboli). Conclusion Bevacizumab and irinotecan is an effective treatment for recurrent glioblastoma multiforme and has moderate toxicity.

Từ khóa


Tài liệu tham khảo

10.1056/NEJMoa043330

10.1056/NEJMoa043331

10.1200/JCO.1999.17.5.1516

10.1002/cncr.11306

10.1023/A:1014532202188

10.1215/15228517-2005-010

10.1200/JCO.1999.17.8.2572

10.1023/A:1023367223575

Lamszus K, Ulbricht U, Matschke J, et al: Levels of soluble vascular endothelial growth factor (VEGF) receptor 1 in astrocytic tumors and its relation to malignancy, vascularity, and VEGF-A. Clin Cancer Res 9:1399,2003-1405,

10.1038/nm0603-669

10.1023/A:1013329832067

10.1056/NEJMoa032691

10.1056/NEJMoa061884

10.1200/JCO.2005.03.4645

10.1056/NEJMoa021491

Stark-Vance V: Bevacizumab and CPT-11 in the treatment of relapsed malignant glioma. Neuro-Oncology 7:369,2005, (abstr 342)

10.1158/1078-0432.CCR-06-2309

10.1200/JCO.1990.8.7.1277

10.1054/bjoc.2000.1316

10.1016/S0093-7754(03)70020-7

10.1215/15228517-2006-025

10.1016/j.critrevonc.2006.06.007

10.1002/cncr.21316

10.1002/cncr.11260

10.1215/S1522851705000451

10.1212/01.WNL.0000140495.33615.CA

10.1200/JCO.2004.06.181

10.1186/1476-4598-5-67

10.1158/0008-5472.CAN-06-1010

10.1038/35025220

10.1158/0008-5472.CAN-04-0074

Winkler F, Kozin SV, Tong RT, et al: Kinetics of vascular normalization by VEGFR2 blockade governs brain tumor response to radiation: Role of oxygenation, angiopoietin-1, and matrix metalloproteinases. Cancer Cell 6:553,2004-563,

Thông tin
Thông tin xuất bản

American Society of Clinical Oncology (ASCO)

Tập 25 Số 30

4722-4729

Thông tin tác giả