title: Dose and schedule study of panitumumab monotherapy in patients with advanced solid malignancies.
abstract: OBJECTIVE
  This phase 1 study evaluated the safety, pharmacokinetics, and activity of panitumumab, a fully human, IgG2 monoclonal antibody that targets the epidermal growth factor receptor in patients with previously treated epidermal growth factor receptor-expressing advanced solid tumors.
  
  
  METHODS
  Sequential cohorts were enrolled to receive four i.v. infusions of panitumumab monotherapy at various doses and schedules. Safety was continuously monitored. Serum samples for pharmacokinetic, immunogenicity, and chemistry assessments were drawn at preset intervals. Tumor response was assessed at week 8.
  
  
  RESULTS
  Ninety-six patients received panitumumab. Median (range) age was 61 years (32-79 years), and 72 (75%) patients were male. Tumor types were 41% colorectal cancer, 22% prostate, 16% renal, 15% non-small cell lung, 3% pancreatic, 3% esophageal/gastroesophageal, and 1% anal. The overall incidence of grade 3 or 4 adverse events was 32% and 7%, respectively. The incidence of skin-related toxicities was dose dependent. No maximum tolerated dose was reached. No human anti-panitumumab antibodies were detected. No investigator-determined panitumumab infusion-related reactions were reported. Serum panitumumab concentrations were similar in the 2.5 mg/kg weekly, 6.0 mg/kg every 2 weeks, and 9.0 mg/kg every 3 weeks dose cohorts. Five of 39 patients (13%) with colorectal cancer had a confirmed partial response, and 9 of 39 patients (23%) with colorectal cancer had stable disease.
  
  
  CONCLUSIONS
  Panitumumab was well tolerated with comparable exposure and safety profiles for the weekly, every 2 weeks, and every 3 weeks administration schedules. Rash and dry skin occurred more frequently in the dose cohorts receiving > or =2.5 mg/kg weekly dose. Panitumumab has single-agent antitumor activity, most notably in patients with advanced colorectal cancer.
authors.affiliation: Georgetown University Medical Center, Washington, DC 20057-1465, USA. Weinerl@georgetown.edu
authors.forename: Louis M
authors.initials: LM
authors.lastname: Weiner
authors.forename: Arie S
authors.initials: AS
authors.lastname: Belldegrun
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Crawford
authors.forename: Anthony W
authors.initials: AW
authors.lastname: Tolcher
authors.forename: Pamela
authors.initials: P
authors.lastname: Lockbaum
authors.forename: Rosalin H
authors.initials: RH
authors.lastname: Arends
authors.forename: Lynn
authors.initials: L
authors.lastname: Navale
authors.forename: Rafael G
authors.initials: RG
authors.lastname: Amado
authors.forename: Gisela
authors.initials: G
authors.lastname: Schwab
authors.forename: Robert A
authors.initials: RA
authors.lastname: Figlin
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D004334:Drug Administration Schedule; D066246:ErbB Receptors / Q000276:immunology / Q000378:metabolism*; D005260:Female; D006801:Humans; D007167:Immunotherapy; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology; D000077544:Panitumumab
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D000077544:Panitumumab; D066246:ErbB Receptors