Vol.:(0123456789) 1 3 Cancer Chemother Pharmacol DOI 10.1007/s00280-017-3405-7 ORIGINAL ARTICLE Phase II study of bi‑weekly temozolomide plus bevacizumab for adult patients with recurrent glioblastoma Michael A. Badruddoja 1,2  · Marjorie Pazzi 1  · Abhay Sanan 1  · Kurt Schroeder 1  · Kevin Kuzma 3  · Thomas Norton 1  · Thomas Scully 1,4  · Daruka Mahadevan 5  · Michael Malek Ahmadi 1,3   Received: 3 May 2017 / Accepted: 16 June 2017 © Springer-Verlag GmbH Germany 2017 Results Overall response rate from diagnosis was 51 weeks, the 6-month progression-free survival was 52%, and median time to tumor progression was 5.5 months. Conclusion Bevacizumab plus bi-weekly temozolomide was well tolerated and may be a salvage regimen to be con- sidered in a subset of patients with recurrent glioblastoma. Keywords Glioblastoma · Temozolomide · Bevacizumab · Methyl-guanine · Methyltransferase Introduction The incidence of malignant primary brain tumors in the US is approximately 20,000 cases per year. A majority of these patients will have glioblastoma, the most malignant variant of glioblastoma [1]. Although there have been several dec- ades of intense research aimed at the discovery and devel- opment of novel active agents and combination of agents for the treatment of glioblastoma, the median survival rate ranges from approximately 12 to 15 months with only 2- to 3-month survival for patients receiving the current standard of care [2]. The standard of care for the management of glioblastoma consists of optimal surgical resection, followed by 6 weeks of radiation therapy concurrently with temozolomide, fol- lowed by adjuvant temozolomide [3]. Based upon two stud- ies [4, 5] in May 2009, the FDA conditionally approved bev- acizumab for the treatment of recurrent glioblastoma. The 6-month progression-free survival (6-month PFS) for these studies was 36% and 29%, with time to tumor progression of 4.2 and 3.9 months, respectively. There are several studies suggesting that alternate scheduled dosing of temozolomide is safe and may potentially lead to further depletion of meth- ylguanine methyltransferase (MGMT) [6–8]. Two studies Abstract Purpose Bevacizumab is an active anti-angiogenic agent in the treatment of recurrent glioblastoma. Temozolomide can prolong survival in patients with newly diagnosed glioblas- toma. At recurrence, alternate dosing of temozolomide has shown to further deplete methyl-guanine-methyltransferase (MGMT) conferring added activity for patients who have progressed on the standard dosing regimen. In this study, bevacizumab plus biweekly temozolomide was evaluated for efcacy in adult patients with recurrent glioblastoma. Methods Thirty patients with recurrent glioblastoma were treated with bevacizumab on (10 mg/kg i.v.) days 1 and 15 of a 28-day cycle combined with temozolomide (100 mg/m 2 ) on days 1–5 and 15–19 on a 28-day cycle. Responses were assessed at week 4 and then every 8 weeks. MGMT status and quality of life measures were also assessed. * Michael A. Badruddoja badru001@neurotucson.com * Daruka Mahadevan dmahadevan@uacc.arizona.edu 1 Center for Neurosciences, 2450 E River Rd, Tucson, AZ 85718, USA 2 Department of Radiation Oncology, Banner University Medical Center, 1501 N. Campbell Avenue, Tucson, AZ 85724, USA 3 Genentech, Inc., DNA Way, South San Francisco, CA 94080, USA 4 Northwest Neurospecialists, 5860 N. La Cholla Blvd. Suite 100, Tucson, AZ 85741, USA 5 University of Arizona Cancer Center, 1515 N. Campbell Avenue, Tucson, AZ 85724, USA