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Phase I Trial of Iodine-131-Chimeric B72.3 (Human IgG4) in Metastatic Colorectal Cancer

Departments of Radiation Oncology, Medicine and Nuclear Medicine, Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, Alabama; Laboratory of Tumor Immunology and Biology, National Cancer Institute, Bethesda, Maryland; and American Cyanamid Co., Pearl River, New York

Correspondence: For reprints contact: Ruby Meredith, MD, PhD, University of Alabama at Birmingham, L.B. Wallace Tumor Institute-117, UAB Station, Birmingham, AL 35294.

ABSTRACT

Twelve patients with metastatic colorectal cancer participated in a Phase I trial of ¹³¹I-labeled chimeric B72.3 (human IgG4). Consecutive groups of patients received 18 mCi/m², 27 mCi/m² and 36 mCi/m². No acute side effects related to antibody administration were noted. Bone marrow suppression was the only side effect; it was dose-dependent and correlated with whole-body radiation dose estimates. The lowest dose level produced no marrow suppression, whereas 27 mCi/m² resulted in Grade 1 and 2 marrow suppression in two of three patients. The maximum tolerated dose was 36 mCi/m² with all six patients at this dose level having at least Grade 1 and two patients with Grade 3 and 4 marrow suppression. Eight of 12 patients had radioimmune imaging of tumor sites at 5–22 days. Seven patients had an antibody response to initial infusion. On retreatment, whole-body kinetics and imaging were altered for patients with a high anti-ch-B72.3 response. Thus, chimeric B72.3 (IgG4) has limited utility as a means of delivering multiple therapeutic doses of ¹³¹I in the majority of patients; alternative strategies including second generation anti-TAG-72 monoclonal antibodies, other radioisotopes and other chimeric human isotypes will need to be pursued.

FOOTNOTES

^* Current address: University of Nebraska, Omaha, Nebraska.

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