title: Phase I trial of iodine 131-labeled COL-1 in patients with gastrointestinal malignancies: influence of serum carcinoembryonic antigen and tumor bulk on pharmacokinetics.
abstract: OBJECTIVE
  COL-1 is a high-affinity murine monoclonal antibody (MAb) 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 (131I) was administered to patients with advanced gastrointestinal (GI) malignancies to evaluate tolerance and pharmacokinetics.
  
  
  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 COL-1 labeled with 131I, with doses from 10 mCi/m2 to 75 mCi/m2. 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 > or = 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 cm2) 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/m2. The correlation between dose (millicuries per square meter) and thrombocytopenia was made stronger, by accounting for either variation in pharmacokinetics, or variation in serum CEA and tumor bulk.
  
  
  CONCLUSIONS
  131I-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 131I-labeled COL-1 more rapidly from the circulation and experience less myelosuppression.
authors.affiliation: Navy Medical Oncology Branch, National Cancer Institute National Institutes of Health, Bethesda, MD USA.
authors.forename: B
authors.initials: B
authors.lastname: Yu
authors.forename: J
authors.initials: J
authors.lastname: Carrasquillo
authors.forename: D
authors.initials: D
authors.lastname: Milenic
authors.forename: Y
authors.initials: Y
authors.lastname: Chung
authors.forename: P
authors.initials: P
authors.lastname: Perentesis
authors.forename: I
authors.initials: I
authors.lastname: Feuerestein
authors.forename: D
authors.initials: D
authors.lastname: Eggensperger
authors.forename: C F
authors.initials: CF
authors.lastname: Qi
authors.forename: C
authors.initials: C
authors.lastname: Paik
authors.forename: J
authors.initials: J
authors.lastname: Reynolds
authors.forename: J
authors.initials: J
authors.lastname: Grem
authors.forename: G
authors.initials: G
authors.lastname: Curt
authors.forename: K
authors.initials: K
authors.lastname: Siler
authors.forename: J
authors.initials: J
authors.lastname: Schlom
authors.forename: C
authors.initials: C
authors.lastname: Allegra
mesh_terms: D000911:Antibodies, Monoclonal; D002272:Carcinoembryonic Antigen / Q000097:blood* / Q000276:immunology; D015179:Colorectal Neoplasms / Q000532:radiotherapy; D004307:Dose-Response Relationship, Radiation; D005770:Gastrointestinal Neoplasms / Q000000981:diagnostic imaging / Q000276:immunology / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D007457:Iodine Radioisotopes / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010190:Pancreatic Neoplasms / Q000532:radiotherapy; D016499:Radioimmunotherapy / Q000009:adverse effects; D011877:Radionuclide Imaging; D011879:Radiotherapy Dosage; D013274:Stomach Neoplasms / Q000532:radiotherapy
chemical_list: D000911:Antibodies, Monoclonal; D002272:Carcinoembryonic Antigen; D007457:Iodine Radioisotopes