Clinical Trials with Interferon-Alpha as a Chemosensitizer in Gliomas

Abstract

To assess the efficacy of recombinant interferon-alpha (IFN-rα) combined with carmustine (BCNU) and other agents, we performed four prospective clinical trials. Of 35 patients with recurrent glioma who were given BCNU and IFN-rα, 29% experienced regression with a median duration of 10.1 months; 37% of nonresponders remained stable for more than 6 months. By contrast, the combination of IFN-rα and alpha-dimethylornithine (DFMO) produced no responses in 29 patients with recurrent glioma. We then completed a phase I study of 15 patients with newly diagnosed grade 3 or 4 glioma [World Health Organization (WHO) classification] treated with radiation, BCNU, and IFN-rα. In that study, IFN-rα 12 × 10⁶ units/ m² s.c. on days 1–3 of each week produced excessive fatigue, weight loss, and confusion, but patients could tolerate IFN-rα at 12 X 10⁶ units/m² given on days 1–3 of weeks 1, 3, and 5 of each 7-week cycle with BCNU given at 150 mg/m² on day 3 every 7 weeks. Eight patients had grade 4 gliomas and 7 had grade 3 gliomas. For the 4 evaluable grade 4 patients, the mean survival time was 24.6 months (range, 12.6–44.7 months); 3 of the 7 grade 3 patients remained alive for 50.2+ to 55.5+ months without tumor recurrence. We are conducting a prospective phase III trial in which all patients first receive radiation plus BCNU then are randomized to BCNU alone or BCNU plus IFN-rα. To date, 383 patients have been registered on the study and 274 have been randomized. Toxicity with the IFN-rα regimen has been pronounced, consisting of flu-like symptoms, confusion, and somnolence. Survival data are not yet sufficiently established to be reported.