A Phase II study of anti-epidermal growth factor receptor radioimmunotherapy in the treatment of glioblastoma multiforme.

OBJECT: This single-institution Phase II study tests the efficacy of adjuvant radioimmunotherapy with (125)I-labeled anti-epidermal growth factor receptor 425 murine monoclonal antibody ((125)I-mAb 425) in patients with newly diagnosed glioblastoma multiforme (GBM). METHODS: A total of 192 patients with GBM were treated with (125)I-mAb 425 over a course of 3 weekly intravenous injections of 1.8 GBq following surgery and radiation therapy. The primary end point was overall survival, and the secondary end point was toxicity. Additional subgroup analyses were performed comparing treatment with (125)I-mAb 425 (RIT, 132 patients), (125)I-mAb 425 and temozolomide (TMZ+RIT, 60 patients), and a historical control group (CTL, 81 patients). RESULTS: The median age was 53 years (range 19-78 years), and the median Karnofsky Performance Scale score was 80 (range 60-100). The percentage of patients who underwent debulking surgery was 77.6% and that of those receiving temozolomide was 31.3%. The overall median survival was 15.7 months (95% CI 13.6-17.8 months). The 1- and 2-year survivals were 62.5 and 25.5%, respectively. For subgroups RIT and TMZ+RIT, the median survivals were 14.5 and 20.2 months, respectively. No Grade 3 or 4 toxicity was seen with the administration of (125)I-mAb 425. The CTL patients lacked Karnofsky Performance Scale scores, had poorer survival, were older, and were less likely to receive radiation therapy. On multivariate analysis, the hazard ratios for RIT versus CTL, TMZ+RIT versus CTL, and TMZ+RIT versus RIT were 0.49 (p < 0.001), 0.30 (p < 0.001), and 0.62 (p = 0.008), respectively. CONCLUSIONS: In this large Phase II study of 192 patients with GBM treated with anti-epidermal growth factor receptor (125)I-mAb 425 radioimmunotherapy, survival was 15.7 months, and treatment was safe and well tolerated.

Radioimmunotherapy as a novel treatment regimen: 125I-labeled monoclonal antibody 425 in the treatment of high-grade brain gliomas.

A Phase I/II clinical trial was undertaken between January 29, 1987 and January 25, 1997 to assess the efficacy of (125)I-labeled monoclonal antibody 425 ((125)I-MAb 425) in controlling high-grade brain gliomas. A total of 180 patients diagnosed with glioblastoma multiforme (GBM) and astrocytoma with anaplastic foci (AAF) were administered (125)I-MAb 425 as an adjuvant treatment. All underwent initial surgery followed by postoperative external beam radiation therapy and a cumulative dose of 140 mCi of (125)I-MAb 425. Biodistribution of radioactivity after antibody administration showed increased uptake in brain tumor cells due to enhanced expression of epidermal growth factor receptors. A longer half-life of (125)I-MAb 425 in brain tumor cells compared to blood was observed. All patients were followed up for at least 5 years. Overall actuarial survival range for GBM and AAF patients showed 4-150 and 4-270 months, respectively. GBM and AAF patients under age 40 years with a Karnofsky performance status >70 had an actuarial median survival of 22.5 and 65 months, respectively. This adjuvant therapy demonstrates a significant increase in median survival and should be considered in the management of high-grade brain gliomas.

Radioiodinated (I-125) monoclonal antibody 425 in the treatment of high grade glioma patients: ten-year synopsis of a novel treatment.

The present report is the follow-up of patients enrolled in a phase II clinical trial using I-MAb 425 as an adjuvant treatment for high grade gliomas. Patient median survivals support published data from an earlier preliminary report. From January 29, 1987 to January 25, 1997, 180 patients diagnosed with astrocytoma with anaplastic foci (AAF) and glioblastoma multiforme (GBM) were treated as outpatients with an average of three weekly intravenous or intraarterial injections of radiolabeled MAb 425. The mean dose was 140 mCi (5.2 GBq). Only one patient who received a single dose of more than 60 mCi (2.2 GBq) experienced acute toxicity. Patients received prior surgery and radiation therapy, with and without chemotherapy. Overall median survival for patients with GBM and AAF was 13.4 and 50.9 months, respectively, with Karnofsky Performance Status (KPS) ranging from 40 to 100 and age ranging from 11 to 75 years. Prognostic factors (KPS and age) correlated positively with increased survival, with KPS the most important determinant of median survival. Data analysis was performed on patients followed 5 years or longer. We conclude that the administration of I-MAb 425 with intensive medical management demonstrates a significant increase in median survival and should be considered a therapeutic regimen for the management of patients with high grade gliomas.