title: Phase I trial of murine monoclonal antibody 14G2a administered by prolonged intravenous infusion in patients with neuroectodermal tumors.
abstract: OBJECTIVE
  The purpose of this phase I trial was to determine the toxicity and maximum-tolerated dose (MTD) of murine monoclonal antibody (Mab) 14G2a (anti-GD2) in cancer patients.
  
  
  METHODS
  Following tracer doses of iodine-131-labeled 14G2a to determine tumor uptake, 18 patients with refractory melanoma, neuroblastoma, or osteosarcoma received unlabeled 14G2a at total concentrations of 50, 100, and 200 mg/m2 administered as daily 24-hour infusions for 5 days.
  
  
  RESULTS
  The overall sensitivity of external immunoscintigraphy was 64 of 74 known metastases (86%). Toxicity from prolonged infusion of 14G2a consisted of severe generalized pain, hyponatremia, fever, rash, paresthesias, weakness, and chronic refractory postural hypotension (two patients). Toxicity was less severe in pediatric patients. The MTD of Mab was 100 mg/m2. Sixteen of 18 patients developed human antimouse antibodies (HAMA) to 14G2a. Terminal-phase half-life (T1/2) of unlabeled Mab was 6.6 +/- 1.8 hours for patients receiving 50 mg/m2 and 39.5 +/- 13.3 hours at the 100-mg/m2 level. Tumor biopsies from six melanoma patients were positive for GD2 antigen, but only two of six had trace amounts of 14G2a present. Three mixed responses (two melanoma, one osteosarcoma) and two partial responses (PRs; neuroblastoma) were observed.
  
  
  CONCLUSIONS
  Mab 14G2a has modest antitumor activity at the expense of significant toxicity. Dose-limiting neurologic sequelae may significantly limit phase II studies other than in pediatric patients with neuroblastoma.
authors.affiliation: Department of Clinical Immunology and Biological Therapy, University of Texas M.D. Anderson Cancer Center, Houston 77030.
authors.forename: J L
authors.initials: JL
authors.lastname: Murray
authors.forename: J E
authors.initials: JE
authors.lastname: Cunningham
authors.forename: H
authors.initials: H
authors.lastname: Brewer
authors.forename: K
authors.initials: K
authors.lastname: Mujoo
authors.forename: A A
authors.initials: AA
authors.lastname: Zukiwski
authors.forename: D A
authors.initials: DA
authors.lastname: Podoloff
authors.forename: L P
authors.initials: LP
authors.lastname: Kasi
authors.forename: V
authors.initials: V
authors.lastname: Bhadkamkar
authors.forename: H A
authors.initials: HA
authors.lastname: Fritsche
authors.forename: R S
authors.initials: RS
authors.lastname: Benjamin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes; D008297:Male; D008545:Melanoma / Q000628:therapy*; D051379:Mice; D008875:Middle Aged; D009447:Neuroblastoma / Q000628:therapy*; D012516:Osteosarcoma / Q000628:therapy*; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D007457:Iodine Radioisotopes