TY - JOUR
T1 - A Phase III study of radiation therapy (RT) and O6-benzylguanine + BCNU versus RT and BCNU alone and methylation status in newly diagnosed glioblastoma and gliosarcoma
T2 - Southwest Oncology Group (SWOG) study S0001
AU - Blumenthal, Deborah T.
AU - Rankin, Cathryn
AU - Stelzer, Keith J.
AU - Spence, Alexander M.
AU - Sloan, Andrew E.
AU - Moore, Dennis F.
AU - Padula, Gilbert D.A.
AU - Schulman, Susan B.
AU - Wade, Mark L.
AU - Rushing, Elisabeth J.
N1 - Publisher Copyright:
© 2014, Japan Society of Clinical Oncology.
PY - 2015/8/8
Y1 - 2015/8/8
N2 - Aims: To determine the efficacy of methylguanine methyltransferase (MGMT) depletion + BCNU [1,3-bis(2-chloroethyl)-1- nitrosourea: carmustine] therapy and the impact of methylation status in adults with glioblastoma multiforme (GBM) and gliosarcoma. Methods: Methylation analysis was performed on GBM patients with adequate tissue samples. Patients with newly diagnosed GBM or gliosarcoma were eligible for this Phase III open-label clinical trial. At registration, patients were randomized to Arm 1, which consisted of therapy with O6-benzylguanine (O6-BG) + BCNU 40 mg/m2 (reduced dose) + radiation therapy (RT) (O6BG + BCNU arm), or Arm 2, which consisted of therapy with BCNU 200 mg/m2 + RT (BCNU arm). Results: A total of 183 patients with newly diagnosed GBM or gliosarcoma from 42 U.S. institutions were enrolled in this study. Of these, 90 eligible patients received O6-BG + BCNU + RT and 89 received BCNU + RT. The trial was halted at the first interim analysis in accordance with the guidelines for stopping the study due to futility (<40 % improvement among patients on the O6BG + BCNU arm). Following adjustment for stratification factors, there was no significant difference in overall survival (OS) or progression-free survival (PFS) between the two groups (one sided p = 0.94 and p = 0.88, respectively). Median OS was 11 [95 % confidence interval (CI) 8–13] months for patients in the O6BG + BCNU arm and 10 (95 % CI 8–12) months for those in the BCNU arm. PFS was 4 months for patients in each arm. Adverse events were reported in both arms, with significantly more grade 4 and 5 events in the experimental arm. Conclusions: The addition of O6-BG to the standard regimen of radiation and BCNU for the treatment patients with newly diagnosed GBM and gliosarcoma did not provide added benefit and in fact caused additional toxicity.
AB - Aims: To determine the efficacy of methylguanine methyltransferase (MGMT) depletion + BCNU [1,3-bis(2-chloroethyl)-1- nitrosourea: carmustine] therapy and the impact of methylation status in adults with glioblastoma multiforme (GBM) and gliosarcoma. Methods: Methylation analysis was performed on GBM patients with adequate tissue samples. Patients with newly diagnosed GBM or gliosarcoma were eligible for this Phase III open-label clinical trial. At registration, patients were randomized to Arm 1, which consisted of therapy with O6-benzylguanine (O6-BG) + BCNU 40 mg/m2 (reduced dose) + radiation therapy (RT) (O6BG + BCNU arm), or Arm 2, which consisted of therapy with BCNU 200 mg/m2 + RT (BCNU arm). Results: A total of 183 patients with newly diagnosed GBM or gliosarcoma from 42 U.S. institutions were enrolled in this study. Of these, 90 eligible patients received O6-BG + BCNU + RT and 89 received BCNU + RT. The trial was halted at the first interim analysis in accordance with the guidelines for stopping the study due to futility (<40 % improvement among patients on the O6BG + BCNU arm). Following adjustment for stratification factors, there was no significant difference in overall survival (OS) or progression-free survival (PFS) between the two groups (one sided p = 0.94 and p = 0.88, respectively). Median OS was 11 [95 % confidence interval (CI) 8–13] months for patients in the O6BG + BCNU arm and 10 (95 % CI 8–12) months for those in the BCNU arm. PFS was 4 months for patients in each arm. Adverse events were reported in both arms, with significantly more grade 4 and 5 events in the experimental arm. Conclusions: The addition of O6-BG to the standard regimen of radiation and BCNU for the treatment patients with newly diagnosed GBM and gliosarcoma did not provide added benefit and in fact caused additional toxicity.
KW - BCNU
KW - Carmustine
KW - Glioblastoma
KW - MGMT
KW - Methylation
KW - SWOG
UR - http://www.scopus.com/inward/record.url?scp=84938745498&partnerID=8YFLogxK
U2 - 10.1007/s10147-014-0769-0
DO - 10.1007/s10147-014-0769-0
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C2 - 25407559
AN - SCOPUS:84938745498
SN - 1341-9625
VL - 20
SP - 650
EP - 658
JO - International Journal of Clinical Oncology
JF - International Journal of Clinical Oncology
IS - 4
ER -
