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Abstract

Combined treatment with interferon-beta, MCNU (Ranimustine), and radiotherapy was assessed in patients with malignant glioma who had not received previous cytotoxic drug therapy. Forty-three patients up to 75 years old with histopathologically confirmed malignant glioma were studied. All patients had tumors measurable by neuroimaging, a Karnofsky performance score exceeding 40, and an expected survival exceeding 2 months. A response rate of 49% (21/45) was observed, including 6 complete remissions (14%) and 15 partial remissions (35%). Of the 43 patients who completed initial therapy, 19 were given sequential maintenance therapy. Survival time was much longer with than without maintenance therapy. Toxic side effects were moderate and did not substantially affect patients' general condition. We concluded that this combination therapy had a pronounced effect on untreated malignant glioma, particularly in patients whose initial therapy was followed up with maintenance therapy.

JCOG0911 INTEGRA study: a randomized screening phase II trial of interferonβ plus temozolomide in comparison with temozolomide alone for newly diagnosed glioblastoma

“…1 ). We determined IFN-beta dosage based on previously published trials, including a Phase I trial [ 11 , 14 , 17 – 20 ].…”

“…In the treatment of malignant gliomas, IFNβ can act as a drug sensitizer, and it enhances the toxicity of chemotherapeutic agents against various neoplasms when administered in combination with nitrosourea [ 10 ]. Combination therapy with IFNβ and nitrosourea has been used primarily in the treatment of gliomas in Japan [ 11 ]. In our previous in vitro study of human glioma cells, we found that IFNβ markedly enhanced chemosensitivity to TMZ [ 12 ].…”

Human SLFN5 is a transcriptional co-repressor of STAT1-mediated interferon responses and promotes the malignant phenotype in glioblastoma

“…Type-I interferons (IFNs), specifically IFN-α and IFN-β, exhibit important antineoplastic properties in vitro and in vivo against a wide variety of malignancies ( 4 , 5 ). There has been some evidence for Type-I IFN antitumor activity in GBM in vitro and in vivo , but this primarily involves studies of IFN combinations with chemotherapeutic agents ( 6 ). IFNβ treatment has been shown to sensitize human glioma cells to temozolomide (TMZ) treatment in vitro ( 7 ), and in some cases may have a beneficial therapeutic effect when incorporated in the therapeutic regimen of GBM patients ( 8 ).…”

Current Trends in Targeted Therapies for Glioblastoma Multiforme

“…In the treatment of malignant gliomas, IFN- β can act as a drug sensitizer by enhancing the toxicity of chemotherapeutic agents against various neoplasms when administered in combination with nitrosoureas. Combination therapy with IFN- β and nitrosoureas is primarily used for the treatment of gliomas in Japan [23]. In a previous in vitro study in human glioma cells, we found that IFN- β markedly enhances chemosensitivity to TMZ [24]; this finding suggests that one of the major mechanisms by which IFN- β enhances chemosensitivity is the downregulation of MGMT transcription via p53 induction.…”