title: Phase I trial of iodine-131-chimeric B72.3 (human IgG4) in metastatic colorectal cancer.
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.
authors.affiliation: Department of Radiation Oncology, University of Alabama, Birmingham 35294.
authors.forename: R F
authors.initials: RF
authors.lastname: Meredith
authors.forename: M B
authors.initials: MB
authors.lastname: Khazaeli
authors.forename: W E
authors.initials: WE
authors.lastname: Plott
authors.forename: M N
authors.initials: MN
authors.lastname: Saleh
authors.forename: T
authors.initials: T
authors.lastname: Liu
authors.forename: L F
authors.initials: LF
authors.lastname: Allen
authors.forename: C D
authors.initials: CD
authors.lastname: Russell
authors.forename: R A
authors.initials: RA
authors.lastname: Orr
authors.forename: D
authors.initials: D
authors.lastname: Colcher
authors.forename: J
authors.initials: J
authors.lastname: Schlom
mesh_terms: D000230:Adenocarcinoma / Q000532:radiotherapy*; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D003110:Colonic Neoplasms / Q000532:radiotherapy*; D004341:Drug Evaluation; D006801:Humans; D007074:Immunoglobulin G / Q000009:adverse effects / Q000627:therapeutic use*; D007457:Iodine Radioisotopes / Q000009:adverse effects / Q000627:therapeutic use*; D007970:Leukopenia / Q000209:etiology; D008113:Liver Neoplasms / Q000532:radiotherapy / Q000556:secondary; D008875:Middle Aged; D011879:Radiotherapy Dosage; D013921:Thrombocytopenia / Q000209:etiology
chemical_list: D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D007457:Iodine Radioisotopes