title: 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.
abstract: 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.
authors.affiliation: Southeast Radiation Oncology Group, Department of Radiation Oncology, Levine Cancer Institute at Carolinas Medical Center, 1021 Morehead Medical Drive, Charlotte, NC, 28204, USA, stuart.burri@carolinashealthcare.org.
authors.forename: Stuart H
authors.initials: SH
authors.lastname: Burri
authors.forename: Roshan S
authors.initials: RS
authors.lastname: Prabhu
authors.forename: Ashley L
authors.initials: AL
authors.lastname: Sumrall
authors.forename: Wendy
authors.initials: W
authors.lastname: Brick
authors.forename: Brian D
authors.initials: BD
authors.lastname: Blaker
authors.forename: Brent E
authors.initials: BE
authors.lastname: Heideman
authors.forename: Peggy
authors.initials: P
authors.lastname: Boltes
authors.forename: Renee
authors.initials: R
authors.lastname: Kelly
authors.forename: James T
authors.initials: JT
authors.lastname: Symanowski
authors.forename: Walter F
authors.initials: WF
authors.lastname: Wiggins
authors.forename: Lynn
authors.initials: L
authors.lastname: Ashby
authors.forename: H James
authors.initials: HJ
authors.lastname: Norton
authors.forename: Kevin
authors.initials: K
authors.lastname: Judy
authors.forename: Anthony L
authors.initials: AL
authors.lastname: Asher
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000401:mortality* / Q000473:pathology / Q000628:therapy*; D002330:Carmustine / Q000008:administration & dosage; D003131:Combined Modality Therapy; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D005500:Follow-Up Studies; D005910:Glioma / Q000401:mortality* / Q000473:pathology / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D011184:Postoperative Period; D011379:Prognosis; D011446:Prospective Studies; D011879:Radiotherapy Dosage; D015996:Survival Rate; D000077204:Temozolomide
chemical_list: D003606:Dacarbazine; D002330:Carmustine; D000077204:Temozolomide