J Neurosurg 69:826-829, 1988 Systemic gamma-interferon therapy for recurrent gliomas M. STEPHEN MAHALEY, JR., M.D., PH.D., LINDA BERTSCH, R.N., SHARON CUSH, R.N., AND G. YANCEY GILLESPIE, PH.D. Divisions of Neurological Surgery, University of Alabama, Birmingham, Alabama, and University of North Carolina, Chapel Hill, North Carolina u," Recombinant gamma-interferon (2 mg/sq m) was administered intravenously twice weekly in 8-week courses to 14 patients with recurrent gliomas. Computerized tomography (CT) evidence of response was seen in only one patient, and stabilization for 12 to 86 weeks was recorded in three. This was a disappointing result, particularly in a series of patients with relatively small initial tumor volumes (less than 50 cu mm on enhanced CT) and Karnofsky functional ratings of 70 or higher. In addition, several instances of toxicity potentially attributable to gamma-interferon were observed. KEY WORDS 9 brain neoplasm 9 glioma 9 interferon 9 toxicity 9 recurrent glioma G AMMA-INTERFERONhas been reported to activate the specific cytotoxicity of lymphocytes against glioma cells in the presence of interleukin-2, 3 to inhibit in vitro growth of glioma cell lines, 25 and to increase the human leukocyte antigen (HLA) DR sur- face antigens and cytoplasmic HLA-DR-specific ribo- nucleic acid (RNA) of glioma cells in vitro. 26'27 Smith and his coworkers administered postoperative intra- ventricular gamma-interferon to three patients, begin- ning 2 months after radiotherapy; one of their patients experienced a gradual reduction in tumor size over 9 months, as observed on computerized tomography (CT) scans (unpublished data). We have previously reported the clinical efficacy of alpha-interferon in the treatment of patients with recurrent gliomas, 12 and are now re- porting our less favorable clinical experience with gamma-interferon. Clinical Material and Methods This study was designed to evaluate the toxicity and possible efficacy of recombinant gamma-interferon (Immuneron) administered systemically to adult pa- tients with recurrent progressive gliomas. To enhance the possibility of efficacy, based upon previous experi- ence with alpha-interferon,~2 only patients with enhanc- ing CT tumor volumes of less than 50 cu cm were treated. Each patient had a Karnofsky rating of 70 or higher. Fifteen patients were admitted into the study. One patient (Case 105) received only two injections of gamma-interferon because of hypotension. The char- acteristics of the patients are shown in Table 1. The dose schedule for gamma-interferon was 2 mg/sq m twice weekly (Monday and Thursday or Tuesday and Friday) for 8 weeks. Unless progression of disease was documented, this schedule was repeated twice, followed by maintenance treatment with 2 mg/sq m once weekly until progression. Patients were hospitalized for the 1st week of treatment and were treated as outpatients thereafter. Baseline evaluations prior to beginning treatment included contrast-enhanced CT scanning, neurological examination, Karnofsky functional rating, complete blood count with differential, platelet count, electrolyte evaluation, liver and renal profile, serum glucose level, urinalysis, electrocardiography, and chest x-ray film. Each patient was followed serially with contrast-en- hanced CT scanning, Karnofsky rating, and neurologi- cal examination monthly as well as repeat blood and urine studies throughout the treatment period. Efficacy of treatment was determined by comparing the enhancing tumor volumes on serial CT scans. The CT scans were determined to indicate response when there was 25% or greater reduction in the enhancing tumor volume compared to the baseline CT scan in the absence of any increase in steroid administration. Sta- ble CT scans were those in which the enhancing tumor volume had less than a 25% increase or decrease in size compared to baseline. Progression of disease on CT scans was determined when the enhancing tumor vol- ume increased 25% or more compared to baseline in 826 J. Neurosurg. / Volume 69/December, 1988