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.