title: Escalating protein doses of chimeric monoclonal antibody MOv18 immunoglobulin G in ovarian carcinoma patients: a phase I study.
abstract: BACKGROUND
  Successful first-line treatment of ovarian cancer does not incite cure. Recurrent disease often shows an increased resistance to chemotherapeutic agents. Therefore, other treatment modalities, like (radio)immunotherapy using tumor-associated monoclonal antibodies, should be considered. Chimeric MOv18 (c-MOv18) localizes well in ovarian carcinoma tissue. We investigated the safety of a single intravenous (i.v.) infusion of increasing doses of c-MOv18 in ovarian carcinoma patients.
  
  
  METHODS
  Fifteen patients received c-MOv18 (from 5 mg to 75 mg). Safety was determined by recording vital signs; by hematological, biochemical, and urinary analyses; and by the human-antichimeric antibody (HACA) response. Five patients received c-MOv18 labeled with a tracer dose of iodine-131 to analyze the pharmacokinetics and biodistribution in blood, urine, and tissue biopsies at surgery.
  
  
  RESULTS
  Administration of c-MOv18 IgG was uneventful. No significant changes in hematological, biochemical, or urine profiles were noted at any time postinjection (p.i). Starting with a dose of 50 mg, all patients experienced side effects, like fever, headache, and nausea/vomiting, maximally Grade II (World Health Organization toxicity scale). No HACA response was found up to 12 weeks p.i. The mean elimination half-life after infusion of 30-75 mg c-MOv18 was significantly higher compared with infusion of 1 mg. Absolute amount of c-MOv18 in carcinoma tissue increased with increasing c-MOv18 doses.
  
  
  CONCLUSIONS
  Intravenous administration of c-MOv18 IgG in a dose up to 75 mg is safe, inducing only minor side effects at doses of 50 mg or higher. In view of the characteristics of c-MOv18, this antibody might be applicable as an unmodified antibody or as an immunoconjugate in the treatment of ovarian carcinomas.
authors.affiliation: Department of Obstetrics and Gynecology, University Hospital Vrije Universiteit, Amsterdam, The Netherlands.
authors.forename: C F
authors.initials: CF
authors.lastname: Molthoff
authors.forename: H M
authors.initials: HM
authors.lastname: Prinssen
authors.forename: P
authors.initials: P
authors.lastname: Kenemans
authors.forename: A C
authors.initials: AC
authors.lastname: van Hof
authors.forename: W
authors.initials: W
authors.lastname: den Hollander
authors.forename: R H
authors.initials: RH
authors.lastname: Verheijen
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use*; D007457:Iodine Radioisotopes / Q000627:therapeutic use; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000532:radiotherapy*; D016499:Radioimmunotherapy; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*; D014018:Tissue Distribution
chemical_list: D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D007457:Iodine Radioisotopes; D011993:Recombinant Fusion Proteins