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Phase I/II trial of 131 I‐MN‐14 F(ab) 2 anti–carcinoembryonic antigen monoclonal antibody in the treatment of patients with metastatic medullary thyroid carcinoma
Author(s) -
Juweid Malik E.,
Hajjar George,
Swayne Lawrence C.,
Sharkey Robert M.,
Suleiman Samer,
Herskovic Thomas,
Pereira Michael,
Rubin Arnold D.,
Goldenberg David M.
Publication year - 1999
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/(sici)1097-0142(19990415)85:8<1828::aid-cncr25>3.0.co;2-h
Subject(s) - medicine , carcinoembryonic antigen , thyroid , bone marrow , medullary cavity , thyroid carcinoma , chemotherapy , radiation therapy , medullary thyroid cancer , monoclonal antibody , gastroenterology , antibody , pathology , cancer , immunology
BACKGROUND Monoclonal antibodies (MAbs) against carcinoembryonic antigen (CEA) have been recognized as targeting agents for medullary thyroid carcinoma (MTC). This Phase I/II study was initiated to determine the safety, maximum tolerated dose (MTD), and therapeutic potential of 131 I‐MN‐14 F(ab) 2 anti‐CEA MAb for patients with metastatic MTC. METHODS Fifteen patients were enrolled in this study. Dose escalation was based on estimates of radiation dose to the bone marrow, and the radioactive dose given was determined by a pretherapy diagnostic study in which 8 mCi (0.6–20 mg) of 131 I‐MN‐14 F(ab) 2 was administered 1 week prior to therapy. RESULTS Three patients received an initial dose of 140 centigray (cGy) to bone marrow, 11 received 180 cGy, and 1 received 220 cGy. Myelosuppression was the only significant treatment‐related dose‐limiting toxicity (DLT), and the MTD appeared to be 180 cGy to the bone marrow. Human antimouse antibodies (HAMA) developed in 8 patients 2–6 weeks after therapy. Seven patients had a median of 55% reduction of tumor markers. One patient showed a dramatic improvement in the mass effect on the airways caused by 3 tumor lesions in the neck, with a 45% reduction of overall tumor burden. The disease has continued to be radiologically stable in 11 of 12 assessable patients for periods ranging from 3+ to 26+ months. CONCLUSIONS Therapy with 131 I‐MN‐14 F(ab) 2 is well tolerated and shows evidence of biochemical and radiologic antitumor activity. HAMA development suggests that humanized MAbs will be required in trials with repeated dose schedules. Further dose escalation, alone or in combination with other therapy modalities, is indicated for future trials, preferably with humanized anti‐CEA MAbs. Cancer 1999;85:1828–42. © 1999 American Cancer Society.