Previous investigators have reported encouraging results for malignant gliomas treated using a combination of human interferon beta (IFN-beta) with nimustine hydrochloride (ACNU) and radiation therapy (termed IAR therapy). This study was undertaken to examine further the efficacy of the IAR regimen followed by maintenance therapy with IFN-beta and ACNU in patients with newly diagnosed malignant astrocytomas. Fifty-eight patients were enrolled onto the trial. IFN-beta (2 x 10(6) IU/m(2)/day x 5 days/week for 8 consecutive weeks) and ACNU (80 mg/m(2) on days 1 and 36) were administered intravenously concomitant with radiation therapy followed by IFN-beta (every 2 weeks) and ACNU (every 6 weeks). Of 33 patients assessable for a response, 11 responded (33%), with 4 complete responses. The estimated median overall survival (OS) was 16 months, with values of 58 and 13 months for anaplastic astrocytoma (AA) and glioblastoma (GB) patients, respectively. The overall progression free survival (PFS) was 11 months, with values of 31 and 7 months for AA and GB patients, respectively. The IAR therapy was safe and well tolerated. Based on a statistical analysis of the factors that affected the PFS and OS, histologic grade, postoperative Karnofsky performance scale (KPS), and extent of surgery were identified as independent predictors. The postoperative KPS stood out as the most powerful prognostic factor, which was also the best predictor for the response to IAR therapy. Our findings suggest a possible benefit for IAR therapy followed by maintenance therapy mainly in AA. In addition, they emphasize the importance of a preserved KPS after cytoreductive surgery, which could produce a potential benefit for adjuvant therapy and could ultimately lead to a prolonged survival.