Phase II study of biweekly temozolomide plus bevacizumab for adult patients with recurrent glioblastoma multiforme.
Authors: M. A. Badruddoja, M. Pazzi, B. Stea, K. M. Kuzma, M. C. Bishop, R. Carmody, K. Schroeder, J. Seeger, M. Marsella, A. Sanan
Journal: Journal of Clinical Oncology (2010)

e12554^ Background: Glioblastoma multiforme (GBM) accounts for half of all primary brain tumors and despite decades of research, median survival is about 8-12 months. Temozolomide (TMZ) is an alkalating agent which is approved as a first-line therapy for GBM. Bevacizumab (BEV) is a monoclonal antibody which targets vascular endothelial growth factor and is approved for the treatment of recurrent GBM. The combination of BEV and standard dosing of TMZ may not increase survival above the use of TMZ alone. Alternate dosing of TMZ has been shown to further increase survival in a sub-set of patients. The purpose of this study is to determine the 6-month progression-free survival of patients with recurrent GBM treated with BEV plus biweekly dosing of TMZ. Secondary end-points include radiographic response, evaluation of toxicity, analysis of tumor DNA (MGMT), and functional assessment of cancer therapy for brain tumors (FACT-Br). Methods: Patients with recurrent GBM were treated with BEV 10 mg/kg in combination with TMZ 100 units/m2 every 2 weeks. Complete patient evaluations were repeated every 4 weeks and MRI scans were repeated every 8 weeks. FACT-Br questionnaires were completed every 8 weeks. Results: Accrual goal is 30 subjects; preliminary data is presented. 5 patients have been accrued to this study thus far. 4 patients are actively enrolled in the study. One patient exited after the first cycle of therapy due to progressive disease, the other four have had partial radiographic responses. One patient has been progression-free for > 7 months; the remainder are currently progression-free after 2 cycles. To date there have been no grade 4 toxicities. The following treatment-emergent grade 3 adverse events have been observed: encephalopathy (epileptic), pulmonary emboli and fatigue. Of these, only pulmonary emboli and fatigue were considered possibly drug-associated. Methylation of MGMT gene was NOT detected in any of the 5 subjects. Conclusions: We conclude that the combination of bevacizumab and temozolomide given bi-monthly is well tolerated and may have efficacy in the treatment of recurrent glioblastoma multiforme. Added safety and efficacy data will be reported as this phase II study progresses. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech Genentech, Schering-Plough Genentech, Schering-Plough Genentech In compliance with the guidelines established by the ASCO Conflict of Interest Policy (J Clin Oncol. 2006 Jan 20;24[3]:519-521) and the Accreditation Council for Continuing Medical Education (ACCME), ASCO strives to promote balance, independence, objectivity, and scientific rigor through disclosure of financial and other interests, and identification and management of potential conflicts. According to the ASCO Conflict of Interest Policy, the following financial and other relationships must be disclosed: employment or leadership position, consultant or advisory role, stock ownership, honoraria, research funding, expert testimony, and other remuneration (J Clin Oncol. 2006 Jan 20;24[3]:520). The ASCO Conflict of Interest Policy disclosure requirements apply to all authors who submit abstracts to the Annual Meeting. For clinical trials that began accrual on or after April 29, 2004, ASCO's Policy places some restrictions on the financial relationships of principal investigators (J Clin Oncol. 2006 Jan 20;24[3]:521). If a principal investigator holds any restricted relationships, his or her abstract will be ineligible for placement in the 2010 Annual Meeting unless the ASCO Ethics Committee grants an exception. Among the circumstances that might justify an exception are that the principal investigator (1) is a widely acknowledged expert in a particular therapeutic area; (2) is the inventor of a unique technology or treatment being evaluated in the clinical trial; or (3) is involved in international clinical oncology research and has acted consistently with recognized international standards of ethics in the conduct of clinical research. NIH-sponsored trials are exempt from the Policy restrictions. Abstracts for which authors requested and have been granted an exception in accordance with ASCO's Policy are designated with a caret symbol (^) in the Annual Meeting Proceedings. For more information about the ASCO Conflict of Interest Policy and the exceptions process, please visit www.asco.org/conflictofinterest.