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

Abstract

BACKGROUND The current study was conducted to determine whether the addition of interferon‐α (IFN‐α) 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/m2 on Day 1) or BCNU (150 mg/m2 on Day 3) plus IFN—α (12 million U/m2 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‐α 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‐α 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. Cancer 2001;92:420–33. © 2001 American Cancer Society.

Antiangiogenic Strategies for Treatment of Malignant Gliomas

“…Several other inhibitors of the FGF pathway had limited efficacy in clinical trials of MG patients, including interferon-␣, 71 Interferon-␤, 72 and suramin. 73,74 However, FGF receptor TKIs with greater specificity for the FGF pathway have been developed; these drugs, which include TKI-258 (Novartis), XL-999 (Exelixis, South San Francisco, California), brivanib (Bristol-Myers Squibb, New York, NY), and BIBF1120 (Boehringer Ingelheim, Germany), have potential utility in MG patients.…”

Sequential delivery of interferon-α gene and DCs to intracranial gliomas promotes an effective antitumor response

“…14,15 IFN-a-transduced tumor cells also activate and promote the survival of tumor-specific CD8 + CTLs in vivo. 16 Although the type I IFN protein has been used therapeutically for patients with malignant gliomas by systemic administration and its safety has been demonstrated, 17,18 it has been difficult to achieve effective cytokine levels within the tumor at clinically tolerated doses. In an effort to target the expression of this cytokine to the tumor cells themselves, type I IFN gene transfer strategies have been examined in murine intracranial (i.c.)…”

Current Immunotherapeutic Strategies for Central Nervous System Tumors

“…IFN-α was tested in a phase III clinical trial for patients with high grade gliomas [47]. The study included 360 patients with AA, anaplastic AO, GBM and gliosarcoma.…”

“…Following radiotherapy, patients without disease progression were stratified and randomized into two groups: BCNU, and BCNU plus INF-α. Unfortunately, there was no difference in response rates between the two treatment arms in the final evaluation [47]. Table 1 summarizes the most recent clinical trials employing various cytokine based regimens against CNS tumors.…”