title: Phase I trial of multiple large doses of murine monoclonal antibody CO17-1A. II. Pharmacokinetics and immune response.
abstract: Twenty-five patients with metastatic gastrointestinal adenocarcinoma received one to four infusions of large doses (400 mg) of murine monoclonal antibody CO17-1A (17-1A). The pharmacokinetics of 17-1A at the time of first, second, third, or fourth infusion were not statistically different; plasma half-lives were 15.0 +/- 1.7 hours (n = 5), 15.1 +/- 1.8 (n = 10), 25.3 +/- 6.2 (n = 3), and 14.4 +/- 1.8 (n = 5), respectively. Most patients had an antibody response to 17-1A, with peak levels occurring 15-22 days after infusion. The presence of serum antibody to 17-1A at the time of the second or third infusion did not significantly alter the pharmacokinetics of this large dose of antibody. Four of 25 patients failed to develop an antibody response, but this did not correlate with the amount of 17-1A administered. The administration of four doses of 400 mg over 1 week provided continuously circulating 17-1A for 10 days.
authors.affiliation: Comprehensive Cancer Center, University of Alabama, Birmingham 35294.
authors.forename: M B
authors.initials: MB
authors.lastname: Khazaeli
authors.forename: M N
authors.initials: MN
authors.lastname: Saleh
authors.forename: R H
authors.initials: RH
authors.lastname: Wheeler
authors.forename: W J
authors.initials: WJ
authors.lastname: Huster
authors.forename: H
authors.initials: H
authors.lastname: Holden
authors.forename: R
authors.initials: R
authors.lastname: Carrano
authors.forename: A F
authors.initials: AF
authors.lastname: LoBuglio
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000032:analysis* / Q000276:immunology; D005770:Gastrointestinal Neoplasms / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D006207:Half-Life; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis; D051379:Mice
chemical_list: D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G