Combination chemoradiotherapy with temozolomide, vincristine, and interferon-β might improve outcomes regardless of O6-methyl-guanine-DNA-methyltransferase (MGMT) promoter methylation status in newly glioblastoma

BMC Cancer. 2021 Jul 28;21(1):867. doi: 10.1186/s12885-021-08592-z.


Background: This investigator-initiated, open-label, single-arm, single-institute study was conducted to investigate the effectiveness of induction combination chemoradiotherapy and long-term maintenance therapy with temozolomide (TMZ) plus interferon (IFN)-β for glioblastoma.

Methods: The initial induction combination chemoradiotherapy comprised radiotherapy plus TMZ plus vincristine plus IFN-β. Maintenance chemotherapy comprised monthly TMZ, continued for 24-50 cycles, plus weekly IFN-β continued for as long as possible. The primary endpoint was 2-year overall survival (2y-OS). The study protocol was to be considered valid if the expected 2y-OS was over 38% and the lower limit of the 95% confidence interval (CI) was no less than 31.7% compared with historical controls, using Kaplan-Meier methods. Secondary endpoints were median progression-free survival (mPFS), median OS (mOS), 5-year OS rate (5y-OS), and mPFS and mOS classified according to MGMT promoter methylation status.

Results: Forty-seven patients were analyzed. The 2y-OS was 40.7% (95%CI, 27.5-55.4%). The mPFS and mOS were 11.0 months and 18.0 months, respectively, and 5y-OS was 20.3% (95%CI, 10.9-34.6%). The mPFS in groups with and without MGMT promoter methylation in the tumor was 10.0 months and 11.0 months (p = 0.59), respectively, and mOS was 24.0 months and 18.0 months (p = 0.88), respectively. The frequency of grade 3/4 neutropenia was 19.1%.

Conclusions: The 2y-OS with induction multidrug combination chemoradiotherapy and long-term maintenance therapy comprising TMZ plus IFN-β tended to exceed that of historical controls, but the lower limit of the 95%CI was below 31.7%. Although the number of cases was small, this protocol may rule out MGMT promoter methylation status as a prognostic factor.

Trial registration: University Hospital Medical Information Network (number UMIN000040599 ).

Keywords: Combination therapy; Interferon-β; MGMT; Newly glioblastoma; Temozolomide.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Chemoradiotherapy* / methods
  • Combined Modality Therapy
  • DNA Methylation*
  • DNA Modification Methylases / genetics*
  • DNA Repair Enzymes / genetics*
  • Female
  • Glioblastoma / genetics*
  • Glioblastoma / mortality
  • Glioblastoma / pathology
  • Glioblastoma / therapy*
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Prognosis
  • Promoter Regions, Genetic*
  • Treatment Outcome
  • Tumor Suppressor Proteins / genetics*
  • Young Adult


  • Tumor Suppressor Proteins
  • DNA Modification Methylases
  • MGMT protein, human
  • DNA Repair Enzymes