title: Cetuximab Pharmacokinetics Influences Overall Survival in Patients With Head and Neck Cancer.
abstract: A retrospective study was conducted to analyze interindividual variability of cetuximab pharmacokinetics and its influence on survival (progression-free survival and overall survival [OS]) in a cohort of head and neck squamous cell carcinoma (HNSCC).
  
  
  
  Thirty-four patients received cetuximab as an infusion loading dose of 400 mg/m followed by weekly infusions of 250 mg/m. Twenty-one patients had locally advanced HNSCC, and 13 had metastatic/recurrent HNSCC. Cetuximab concentrations were measured by the enzyme-linked immunosorbent assay, and its pharmacokinetics was analyzed by a population approach. Survivals were analyzed with the log-rank test.
  
  
  
  Cetuximab pharmacokinetics was best described using a 2-compartment model with both first-order and saturable (zero-order) eliminations. Estimated pharmacokinetic parameters (%CV) were central volume of distribution V1 = 3.18 L (6%), peripheral volume of distribution V2 = 5.4 L (42%), elimination clearance CL = 0.57 L/d (31%), distribution clearance Q = 0.64 L/d, and zero-order elimination rate k0 = 6.72 mg/d (29%). Both V1 and V2 increased with the body surface area. Adjunction of chemotherapy reduced CL and increased k0. OS was inversely related with cetuximab global clearance (P = 0.007) and was higher in patients with severe radiation dermatitis (P = 0.005).
  
  
  
  Cetuximab pharmacokinetics in patients with HNSCC can be described using a 2-compartment model combining linear and nonlinear mechanisms of elimination. OS is associated with both cetuximab global clearance and severe radiation dermatitis.
authors.affiliation: *Université François-Rabelais de Tours; †Service de Radiothérapie, CHRU de Tours; and ‡Laboratoire de Pharmacologie-Toxicologie, CHRU de Tours, France.
authors.forename: Yoann
authors.initials: Y
authors.lastname: Pointreau
authors.forename: Nicolas
authors.initials: N
authors.lastname: Azzopardi
authors.forename: David
authors.initials: D
authors.lastname: Ternant
authors.forename: Gilles
authors.initials: G
authors.lastname: Calais
authors.forename: Gilles
authors.initials: G
authors.lastname: Paintaud
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D000068818:Cetuximab / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D006258:Head and Neck Neoplasms / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D012189:Retrospective Studies; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000068818:Cetuximab