Two murine monoclonal antibodies, BC-2 and BC-4, raised against tenascin and labeled with 131I were infused locally in the site of neoplastic disease by means of a removable (16 patients) or indwelling (34 patients) catheter. Fifty patients bearing a malignant glioma were treated. Twenty-six of these were suffering from recurrent disease; their tumors relapsed within 9 months (median) after treatment. The remaining 24 cases had a newly diagnosed tumor, and local radioimmunotherapy (RIT) was given immediately after surgery and radiochemotherapy. All efforts were made to reduce the tumor before the infusion of the radiopharmaceutical. Therefore, 22 cases with relapsing glioma underwent additional debulking surgery, which led to total or subtotal removal of tumor in 9 of the patients. Altogether, 28 patients had intralesional RIT when the disease was minimal or microscopic. Conversely, 22 cases underwent local RIT with a tumor the diameter of which was >2 cm. In many cases, the infusions were repeated up to six times to achieve complete destruction of the neoplastic tissue. The local treatment did not give rise to systemic or to cerebral adverse effects. The labeled monoclonal antibodies, given directly in the site of the lesion, concentrated in very high amount in the neoplastic tissue and remained fixed in the target for a long period of time. For these reasons, the radiation dose to the tumor was remarkable (on average >30,000 cGy/cycle) and consequently led to promising results. The median survival was, in total, 20 months (18 in recurrent tumors and 23 in newly diagnosed lesions). Moreover, median survival was 17 months in patients with bulky tumors (both recurrent and newly diagnosed tumors) and 26 months in patients with minimal or microscopic disease. The median time to progression was 3 months in recurrent and 7 months in newly diagnosed gliomas. Finally, RIT produced 3 CRs (all in recurrent tumors), 6 PRs (4 in recurrent and 2 in newly diagnosed), and 11 stabilizations of disease (4 in recurrent and 7 in newly diagnosed). In 19 cases (13 recurrent and 6 newly diagnosed) the progression of tumor was recorded.
Eleven patients (2 recurrent and 9 newly diagnosed) who were treated by RIT when their disease was minimal and nondetectable by radiological methods remained disease-free and were classified as NED. The overall response rate (NED plus CR plus PR) was 40% (34.6% recurrent and 45.8% newly diagnosed). These data provide evidence for the capability of this new therapeutic technique to achieve, in a significant number of cases, lasting control of malignant gliomas and suggest the opportunity to apply this treatment in an adjuvant setting.
Presented at the “Fifth Conference on Radioimmunodetection and Radioimmunotherapy of Cancer,” October 6–8, 1994, Princeton, NJ. This work was supported by a Istituto Oncologico Romagnolo, Cesena (Italy) grant from the National Research Council Program: Clinical Applications in Oncology.