The outcome for patients with glioblastoma multiforme, the most common primary malignant brain tumor, remains dismal. Median survival with current therapy including surgery, radiotherapy and chemotherapy remains 40-50 weeks from diagnosis while available salvage therapies are ineffective following recurrence. Most cases progress at the primary site indicating that local control is the critical first step to improve outcome. In response to the dire need for effective, innovative therapies for patients with malignant brain tumors, our center has developed radiolabeled monoclonal antibodies (mAB) that specifically target tumor antigens. 81C6, a murine IgG2b mAB reacts with an isoform of the extracellular matrix protein tenascin which is highly upregulated and expressed by malignant glioma. Previously completed phase I and II studies in which a fixed dose of 131I-labeled 81C6 was administered directly into the surgical created resection cavity (SCRC), confirmed that this approach improves survival for patients with malignant glioma with acceptable toxicity. A key observation from dosimetry studies accompanying these trials is the demonstration that outcome correlated most closely with delivered dose to the SCRC perimeter. Specifically, patients who received less than 44 Gy to the SCRC perimeter had minimal toxicity from radionecrosis but had a higher rate of tumor recurrence. Conversely those patients who received more than 44 Gy had a lower rate of tumor recurrence but a higher rate of symptomatic radionecrosis. Our HYPOTHESIS is that our phase II study with 131I -81C6 administered to deliver 44 Gy to the 2 cm SCRC perimeter will improve survival of patients with newly diagnosed malignant glioma while minimizing radiation injury to normal CNS tissue.
The SPECIFIC AIMS of this proposal are:
Specific Aim 1. To define the efficacy of 131I -labeled anti-tenascin monoclonal antibody 81C6 administered at a dose to deliver 44 Gy to the 2 cm perimeter of resection cavity of patients with newly diagnosed malignant glioma;
Specific Aim 2. To further define the toxicity of this approach and Specific Aim 3.To determine the impact of this therapy on quality of life.
