Interferon-α2a and 13-cis-retinoic acid with radiation treatment for high-grade glioma

Abstract

Interferon-alpha (IFN-alpha) has been safely given concurrently with radiation therapy (RT) in treating gliomas. As single agents, both IFN-alpha and cis-retinoic acid (CRA) have produced objective tumor regressions in patients with recurrent gliomas. In vitro, IFN-alpha2a and CRA enhance radiation therapy effects on glioblastoma cells more than either agent alone. This trial was conducted to determine the clinical effects of IFN-alpha2a and CRA when given concurrently with radiation therapy to patients with high-grade glioma. Newly diagnosed patients with high-grade glioma received IFN-alpha2a at a dosage of 3 to 6 million IU s.c. 4 times a day for 3 days per week and 1 mg/kg CRA by mouth 4 times a day for 5 days per week during the delivery of partial brain radiation therapy at 180 cGy x 33 fractions for 5 days per week for a total of 59.4 Gy during the 7-week period. Use of the antiepileptic phenytoin was prohibited after observing that the combination of IFN-alpha2a, CRA, and phenytoin was associated with a high rate of dermatologic toxicity not seen in a previous study with concurrent IFN-alpha2a and radiation therapy. Forty patients (26 men and 14 women) with a median age of 60 (range, 19 to 81 years) were enrolled between August 1996 and October 1998. Histopathologic diagnoses were glioblastoma multiforme or grade 4 anaplastic astrocytoma in 36 patients, and grade 3 anaplastic astrocytoma in 4 patients. Only 4 patients (10%) underwent a gross total resection of tumor prior to this therapy; 50% were asymptomatic when treatment was initiated. The planned 7-week course of concurrent therapy was completed by 75% of patients; 30% completed the 16-week course of IFN-alpha and CRA alone. At a median follow-up of 36 months, there were 37 deaths, with a median overall survival of 9.3 months and a 1-year survival rate of 42%. There was no improvement in survival compared with a similar group of 19 patients treated with concurrent IFN-alpha2a and radiation therapy in a previous trial. In the high-risk group of patients in the present study, concurrent treatment with IFN-alpha2a, CRA, and RT was feasible, but was not associated with a better outcome compared with a similar patient population treated with radiation therapy and IFN-alpha2a, or compared with radiation therapy alone in other trials.

Combination celecoxib and temozolomide in C6 rat glioma orthotopic model

“…However, partial responses and prolonged disease stability have occurred with several agents. They are often combined with cytotoxic agents for the treatment of glioblastoma (14)(15)(16)(17).…”

Long-Term Outcome of Postoperative Irradiation in Patients with Newly Diagnosed WHO Grade III Anaplastic Gliomas

“…Pre-RT chemotherapy with carmustine, oral etoposide and cisplatin was insufficiently active, while substantial grade III and IV toxicity was observed in 48% of patients in one study 46 . Antiangiogenic substances such as interferonalpha did not confer any benefit 47,48 .…”

No role of IFITM3 in brain tumor formationin vivo

“…Addition of IFN-α to IR plus carmustine chemotherapy did not improve the survival of newly-diagnosed high-grade glioma patients [ 46 ]. Moreover, the combination of IFN-α and 13-cis-retinoic acid enhanced glioma susceptibility to IR in vitro but did not result in a better outcome in patients treated with IR plus IFN-α as compared to IR alone [ 47 ].…”