BCNU Wafer Placement With Temozolomide (TMZ) in the Immediate Postoperative Period After Tumor Resection Followed by Radiation Therapy With TMZ in Patients With Newly Diagnosed High Grade Glioma: Final Results of a Prospective Multi-Institutional Phase II Trial
Temozolomide (TMZ) and BCNU have demonstrated anti-glioma synergism in preclinical models. We report final data from a prospective, multi-institutional study of BCNU wafers and early TMZ followed by radiation therapy with TMZ in patients with newly diagnosed malignant glioma. 65 patients were consented in 4 institutions, and 46 patients (43 GBM, 3 AA) were eligible for analysis. After resection and BCNU wafer placement, TMZ began on day four postoperatively. Radiation and TMZ (RT/TMZ) were then administered, followed by monthly TMZ at 200 mg/m2 for the first 26 patients, which was reduced to 150 mg/m2 for the remaining 20 patients. Non-hematologic toxicities were minimal. Nine of 27 patients (33 %) who received 200 mg/m2 TMZ, but only 1 of 20 (5 %) who received 150 mg/m2, experienced grade 3/4 thrombocytopenia. Median progression free survival (PFS) and overall survival (OS) period was 8.5 and 18 months, respectively. The 1-year OS rate was 76 %, which is a significant improvement compared with the historical control 1-year OS rate of 59 % (p = 0.023). However, there was no difference in 1-year OS compared with standard RT/TMZ (p = 0.12) or BCNU wafer followed by RT/TMZ (p = 0.87) in post hoc analyses. Early post-operative TMZ can be safely administered with BCNU wafers following resection of malignant glioma at the 150 mg/m2 dose level. Although there was an OS benefit compared to historical control, there was no indication of benefit for BCNU wafers and early TMZ in addition to standard RT/TMZ or early TMZ in addition to regimens of BCNU wafers followed by RT/TMZ.
Medical Subject Headings
Journal of Neuro-Oncology
Digital Object Identifier (DOI)
Burri, Stuart H.; Prabhu, Roshan S.; Sumrall, Ashley L.; Brick, Wendy; Blaker, Brian D.; Heideman, Brent E.; Boltes, Peggy; Kelly, Renee; Symanowski, James T.; Wiggins, Walter F.; Ashby, Lynn S.; Norton, H. James; Judy, Kevin; and Asher, Anthony L., "BCNU Wafer Placement With Temozolomide (TMZ) in the Immediate Postoperative Period After Tumor Resection Followed by Radiation Therapy With TMZ in Patients With Newly Diagnosed High Grade Glioma: Final Results of a Prospective Multi-Institutional Phase II Trial" (2015). Neurology. 3.