Current treatment strategies in patients with newly-diagnosed glioblastoma 
include surgical resection with post-operative radiotherapy and 
concomitant/adjuvant temozolomide (the "Stupp protocol") or resection with 
implantation of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) wafers in the 
surgical cavity followed by radiotherapy. In clinical practice, patients with 
malignant glioma treated with BCNU wafer often also receive adjuvant 
temozolomide. However, current treatment guidelines are unclear on whether and 
how these treatment practices can be combined, and no prospective phase 3 study 
has assessed the safety and efficacy of combining BCNU wafers with temozolomide 
and radiation in high-grade malignant glioma. The rationale for multimodal 
therapy comprising surgical resection with adjunct local BCNU wafers followed by 
radiotherapy and temozolomide is based on complementary and synergistic 
mechanisms of action between BCNU and temozolomide in preclinical studies; a 
shared primary resistance pathway, methylguanine-DNA methyltransferase (MGMT); 
and the opportunity to overcome resistance through MGMT depletion to boost 
cytotoxic activity. A comprehensive review of the literature identified 19 
retrospective and prospective studies investigating the use of this multimodal 
strategy. Median overall survival in 14 studies of newly-diagnosed patients 
suggested a modest improvement versus resection followed by Stupp protocol or 
resection with BCNU wafers, with an acceptable and manageable safety profile.