A Phase I radioimmunotherapy (RAIT) trial will be studied in patients with medullary thyroid cancer (MTC) using the F(ab)2 of an I-131- labeled murine monoclonal antibody (MAb) against carcinoembryonic antigen (CEA). Currently, no effective chemotherapy is available for MTC, and radiation therapy is only effective in controlling local growth. In addition to expressing calcitonin, many MTC express CEA. Pilot clinical studies in patients with advanced MTC have indicated excellent tumor targeting with MN-14 F(ab)2, and favorable dosimetry suggesting the potential for delivering 5000 cGy to tumor sites. Indeed, 2/4 patients studied in a pilot therapy trial had evidence of clinical responses to RAIT treatment. In this study, patients will receive a diagnostic imaging dose of labeled MN-14 F(ab)2 which will be used to confirm antibody targeting, as well as provide radiation dose estimates to the tumor and red marrow. Pharmacokinetic studies will be performed, in addition to daily imaging which will provide important information concerning the kinetics of tumor accretion and retention time. The dose level of radiolabeled MN-14 fragment given for therapy will be adjusted to deliver a desired radiation dose to the red marrow, initially starting at 200 cGy and escalating in 75 cGy increments. Pharmacokinetics for the therapy injection will be compared to that of the diagnostic dose to determine the reliability of these predictions, and imaging when the patient's total body activity is less than 5 mR/h at 1 meter will be used to compare targeting predictions. Once the maximum tolerated dose is determined, they will be able to design and execute a Phase II trial to treat medullary thyroid cancer aggressively, either with the assistance of stem cell support, which will allow for further escalation of activity in patients with advanced disease, or even as an adjuvant following primary surgery.
