title: Dual inhibition of the epidermal growth factor receptor pathway with cetuximab and erlotinib: a phase I study in patients with advanced solid malignancies.
abstract: OBJECTIVE
  To determine the optimal dose of the antiepidermal growth factor receptor (EGFR) monoclonal antibody cetuximab that can be safely administered in combination with a standard daily dose of erlotinib in patients with advanced solid malignancies.
  
  
  METHODS
  Patients with advanced solid malignancies who had failed standard chemotherapies received escalating doses of cetuximab without a loading dose (100, 200, 250 mg/m(2) i.v. weekly) in combination with a fixed dose of erlotinib (150 mg daily orally) until disease progression or unacceptable toxicity.
  
  
  RESULTS
  Twenty-two patients were treated, including 14 patients (64%) with non-small cell lung cancer. Twenty patients received combination treatment at the highest dose level for a median of 5.5 weeks (range, 1-31 weeks). One dose-limiting toxicity was observed: grade 3 skin rash. Overall, the most common adverse events (any grade, grade 3/4) were consistent with the safety profiles of the individual drugs: acneform rash (100%, 9%), diarrhea (77%, 5%), and hypomagnesemia (59%, 12%). Seven of 18 evaluable patients (38.9%) had stable disease lasting for a median of 16.6 weeks (range, 6.1-25.1 weeks).
  
  
  CONCLUSIONS
  Dual EGFR inhibition with cetuximab and erlotinib is feasible; the observed toxicities were manageable and consistent with the safety profiles of the individual drugs. The recommended doses for phase II studies are 250 mg/m(2) i.v. weekly for cetuximab and 150 mg daily orally for erlotinib.
authors.affiliation: Helen F Graham Cancer Center, Newark, DE 19713, USA. mguarino@cbg.org
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Guarino
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Schneider
authors.forename: Martha A
authors.initials: MA
authors.lastname: Hosford
authors.forename: Julie R
authors.initials: JR
authors.lastname: Brahmer
authors.forename: Charles M
authors.initials: CM
authors.lastname: Rudin
authors.forename: Friedrich Graf
authors.initials: FG
authors.lastname: Finckenstein
authors.forename: Robyn E
authors.initials: RE
authors.lastname: Philip-Norton
authors.forename: Haolan
authors.initials: H
authors.lastname: Lu
authors.forename: Martin R
authors.initials: MR
authors.lastname: Weber
authors.forename: David S
authors.initials: DS
authors.lastname: Ettinger
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068818:Cetuximab; D004305:Dose-Response Relationship, Drug; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000069347:Erlotinib Hydrochloride; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors; D000068818:Cetuximab