Phase I trial of iodine 131-labeled COL-1 in patients with gastrointestinal malignancies: Influence of serum carcinoembryonic antigen and tumor bulk on pharmacokinetics

Purpose: COL-1 is a high-affinity murine monoclonal antibody (MAg) specific for carcinoembryonic antigen (CEA). A phase I trial was conducted in which a uniform quantity of antibody labeled with escalating doses of iodine 131 (I-131) was administered to patients with advanced gastrointestinal (GI) malignancies to evaluate tolerance and pharmacokinetics. Patients and Methods: Eighteen patients with advanced, assessable GI malignancies (16 colon, one pancreas, and one gastric) previously treated with conventional chemotherapy (but no pelvic radiation) received 20 mg of OL-1 labeled with I-131, with doses from 10 mCi/m(2) to 75 mCi/m(2), in this cohort, the baseline serum CEA level ranged from 6 to 2,739 ng/mL (mean +/- SD, 500 +/- 639). Results: Nuclear imaging detected at least one tumor site in all 18 patients; 82% of all tumor involved organs were positive and 58% of all lesions greater than or equal to 1.0 cm were detected. Immune complexes were detected in 89% of patients 5 minutes after completion of infusion, and levels correlated with CEA levels (r = .71). Elevated CEA (> 500 ng/mL) and tumor bulk (total tumor area > 150 cm(2)) correlated directly with clearance of serum radioactivity and inversely with serum half-life and cumulative serum radioactivity parameters. Nonhematologic toxicity was mild and non-dose-limiting. Hematologic toxicity, particularly thrombocytopenia, was both dose-related and dose-limiting, The maximal-tolerated dose is 65 mCi/m(2), The correlation between dose (millicuries per square meter) and thrombocytopenia was melds stronger, by accounting for either variation in pharmacokinetics, or variation in serum CEA and tumor bulk. Conclusion: I-131-COL-1 is well tolerated, except for hematologic toxicity. These data suggest that patients with highly elevated circulating CEA levels and/or increased tumor bulk may clear I-131-labeled COL-1 more rapidly from the circulation and experience less myelosuppression.