A phase III study of radiation therapy plus carmustine with or without recombinant interferon-alpha in the treatment of patients with newly diagnosed high-grade glioma

Cancer. 2001 Jul 15;92(2):420-33. doi: 10.1002/1097-0142(20010715)92:2<420::aid-cncr1338>3.0.co;2-3.

Abstract

Background: The current study was conducted to determine whether the addition of interferon-alpha (IFN-alpha) to treatment with radiation therapy and carmustine (BCNU) improves time to disease progression or overall survival in patients with high-grade glioma.

Methods: Patients with anaplastic astrocytoma, anaplastic oligoastrocytoma, glioblastoma multiforme, or gliosarcoma received radiation therapy plus BCNU as initial therapy. Subsequently, patients without tumor progression at the completion of radiation therapy were stratified by age, extent of surgery, tumor grade and histology, Eastern Cooperative Oncology Group performance status, and treating institution, and then were randomly assigned to receive either BCNU alone (200 mg/m(2) on Day 1) or BCNU (150 mg/m(2) on Day 3) plus IFN--alpha (12 million U/m(2) on Days 1-3, Weeks 1, 3, and 5) every 7 weeks for a maximum of 6 cycles.

Results: Of the 383 patients enrolled in the study, 275 eligible patients were randomized. There was no significant difference with regard to time to disease progression or overall survival between the two groups. Patients receiving IFN-alpha experienced more fever, chills, myalgias, and neurocortical symptoms including somnolence, confusion, and exacerbation of neurologic deficits. Cox multivariate regression models confirmed known favorable prognostic variables including younger age, Grade 3 tumor (according to World Health Organization criteria), and greater extent of surgery. Cox and classification and regression tree analysis models also demonstrated that a normal baseline Folstein mini-mental status examination (MMSE) score was associated with better prognosis.

Conclusions: IFN-alpha does not appear to improve time to disease progression or overall survival in patients with high-grade glioma and appears to add significantly to toxicity. The baseline MMSE score may serve as an independent prognostic factor and warrants further investigation.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents, Alkylating / administration & dosage
  • Antineoplastic Agents, Alkylating / pharmacology*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / pathology
  • Brain Neoplasms / radiotherapy*
  • Carmustine / administration & dosage
  • Carmustine / pharmacology*
  • Combined Modality Therapy
  • Disease Progression
  • Female
  • Glioma / drug therapy*
  • Glioma / pathology
  • Glioma / radiotherapy*
  • Humans
  • Interferon-alpha / administration & dosage
  • Interferon-alpha / pharmacology*
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Survival Analysis
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Antineoplastic Agents, Alkylating
  • Interferon-alpha
  • Carmustine