Bevacizumab Plus Irinotecan in Recurrent WHO Grade 3 Malignant Gliomas

• Published in: Clinical cancer research Vol. 14; no. 21; pp. 7068 - 7073
• Main Authors: DESJARDINS, Annick, REARDON, David A, SIGNER, Darell D, FRIEDMAN, Allan H, FRIEDMAN, Henry S, VREDENBURGH, James J, HERNDON, James E, MARCELLO, Jennifer, QUINN, Jennifer A, RICH, Jeremy N, SATHORNSUMETEE, Sith, GURURANGAN, Sridharan, SAMPSON, John, BAILEY, Leighann
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.11.2008
• Subjects: Adult; anaplastic astrocytoma; anaplastic oligodendroglioma; Angiogenesis Inhibitors - administration & dosage; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal, Humanized; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Bevacizumab; Biological and medical sciences; Brain Neoplasms - drug therapy; Brain Neoplasms - mortality; Brain Neoplasms - pathology; Camptothecin - administration & dosage; Camptothecin - analogs & derivatives; Chemotherapy; Cohort Studies; Disease-Free Survival; DNA Topoisomerases, Type I - administration & dosage; Female; Glioma - drug therapy; Glioma - mortality; Glioma - pathology; Humans; Irinotecan; Male; malignant gliomas; Medical sciences; Middle Aged; Neurology; Pharmacology. Drug treatments; Recurrence; Survival Analysis; Tumors of the nervous system. Phacomatoses; Camptothecin derivatives; Antineoplastic agent; Histological grading; Nervous system diseases; Drug combination; Relapse; Enzyme; DNA topoisomerase; Enzyme inhibitor; Monoclonal antibody; Malignant tumor; Bevacizumab; Malignant glioma; Irinotecan; Chemotherapy; Isomerases; Treatment; Vascular endothelium growth factor; Central nervous system disease; Antiangiogenic agent; Topoisomerase I inhibitor; Cancer
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-08-0260

Purpose: Although patients with newly diagnosed WHO grade 3 malignant glioma have a more favorable prognosis than those with WHO grade 4 malignant glioma, salvage therapies following recurrence offer essentially palliative benefit. We did a phase II trial of bevacizumab, a monoclonal antibody to vascular endothelial growth factor, in combination with irinotecan for patients with recurrent grade 3 malignant glioma. Experimental Design: Upon documentation of adequate safety among an initial cohort of nine patients treated with bevacizumab (10 mg/kg) and irinotecan every 14 days, a second cohort ( n = 24) was treated with bevacizumab (15 mg/kg) every 3 weeks with irinotecan on days 1, 8, 22, and 29 of each 42-day cycle. For both cohorts, the dose of irinotecan was 340 mg/m 2 for patients on enzyme-inducing antiepileptic drugs (EIAED) and 125 mg/m 2 for patients not on EIAEDs. After each 6-week cycle, patients were evaluated with a physical examination and magnetic resonance imaging. Results: The 6-month progression-free survival was 55% (95% confidence interval, 36-70%). The 6-month overall survival was 79% (95% confidence interval, 61-89%). Twenty patients (61%) had at least a partial response. Outcome did not differ between the two treatment cohorts. Significant adverse events were infrequent and included a central nervous system hemorrhage in one patient, and one patient who developed thrombotic thrombocytopenic purpura. Conclusion: Bevacizumab and irinotecan is an active regimen with acceptable toxicity for patients with recurrent WHO grade 3 malignant glioma.