Interferon-alpha 2a and 13-cis-retinoic acid with radiation treatment for high-grade glioma

Interferon-alpha (IFN-alpha) has been safely given concurrently with radiat ion therapy (RT) in treating gliomas. As single agents, both IFN-alpha and cis-retinoic acid (CRA) have produced objective tumor regressions in patien ts with recurrent gliomas. In vitro, IFN-alpha 2a and CRA enhance radiation therapy effects on glioblastoma cells more than either agent alone. This t rial was conducted to determine the clinical effects of IFN-alpha 2a and CR A when given concurrently with radiation therapy to patients with high-grad e glioma. Newly diagnosed patients with high-grade glioma received IFN-alph a 2a at a dosage of 3 to 6 miuion 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 deli very of partial brain radiation therapy at 180 cGy x 33 fractions for 5 day s per week for a total of 59.4 Gy during the 7-week period. Use of the anti epileptic phenytoin was prohibited after observing that the combination of IFN-alpha 2a, CRA, and phenytoin was associated with a high rate of dermato logic toxicity not seen in a previous study with concurrent IFN-alpha 2a an d radiation therapy. Forty patients (26 men and 14 women) with a median age of 60 (range, 19 to sl years) were enrolled between August 1996 and Octobe r 1998. Histopathologic diagnoses were glioblastoma multiforme or grade 4 a naplastic astrocytoma in 36 patients, and grade 3 anaplastic astrocytoma in 4 patients. Only 4 patients (10%) underwent a gross total resection of tum or prior to this therapy; 50% were asymptomatic when treatment was initiate d. 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 imp rovement in survival compared with a similar group of 19 patients treated w ith concurrent IFN-alpha 2a and radiation therapy in a previous trial. In t he highrisk group of patients in the present study, concurrent treatment wi th IFN-alpha 2a, CRA, and RT was feasible, but was not associated with a be tter outcome compared with a similar patient population treated with radiat ion therapy and IFN-alpha 2a, or compared with radiation therapy alone in o ther trials.