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A Phase I Trial Combining High-Dose ⁹⁰Y-Labeled Humanized Anti-CEA Monoclonal Antibody with Doxorubicin and Peripheral Blood Stem Cell Rescue in Advanced Medullary Thyroid Cancer

¹ Center for Molecular Medicine and Immunology, Garden State Cancer Center, Belleville, New Jersey
² St. Joseph’s Hospital and Medical Center, Paterson, New Jersey

This trial determined the pharmacokinetics, dosimetry, and dose-limiting toxicity of ⁹⁰Y-hMN-14 IgG (humanized anticarcinoembryonic antigen [CEA, or CEACAM5] monoclonal antibody; labetuzumab), combined with doxorubicin and peripheral blood stem cell (PBSC) support in advanced medullary thyroid cancer (MTC) patients. Methods: Fifteen patients received an infusion of ¹¹¹In-hMN-14 IgG. One to 2 wk later, 14 patients received ⁹⁰Y-hMN-14 IgG, starting at 740 MBq/m², followed 24 h later with a fixed intravenous bolus dose of doxorubicin (60 mg/m²). Preharvested PBSCs were reinfused when the ⁹⁰Y activity in the body was 111 MBq/m². Results: The mean red marrow dose estimated for the ⁹⁰Y-hMN-14 IgG was 1.65 ± 0.59 mGy/MBq (n = 11), with normal organs ranging from 2.3 to 4.4 mGy/MBq. Eighty percent of all known lesions (125/156), including 78 of 79 bone and 16 putatively occult lesions, were targeted. The average radiation dose to the tumor was 15.1 ± 10.8 mGy/MBq (55.8 ± 39.8 cGy/mCi) ⁹⁰Y-hMN-4 IgG (n = 29 tumors in 8 patients), with a majority of the lesions receiving >2,000 cGy at an administered dose of 1,480 MBq/m². The average tumor-to-red marrow, tumor-to-liver, tumor-to-lungs, and tumor-to-kidneys ratios were 15.0 ± 11.0, 5.1 ± 3.6, 6.9 ± 6.1, and 9.0 ± 8.7, respectively. Cardiopulmonary toxicity was dose limiting at 1,850 MBq/m². Minor responses were noted in 2 patients and 1 patient had a partial response (68% reduction in local and hepatic metastatic disease). Conclusion: This treatment combination was well tolerated with complete recovery of blood counts and reversible nonhematologic toxicities at the maximum tolerated dose of 1,480 MBq/m². Evidence of antitumor response in these patients with advanced cancer was modest, but encouraging; this type of treatment may be more successful if applied to more limited, earlier-stage disease.

Key Words: carcinoembryonic antigen • medullary thyroid cancer • radioimmunotherapy • chemotherapy • dosimetry • monoclonal antibody

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