title: A phase II study of lapatinib in recurrent/metastatic squamous cell carcinoma of the head and neck.
abstract: OBJECTIVE
  This study sought to determine the efficacy and safety profile of lapatinib in patients with recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN).
  
  
  METHODS
  This phase II multiinstitutional study enrolled patients with recurrent/metastatic SCCHN into two cohorts: those without (arm A) and those with (arm B) before exposure to an epidermal growth factor receptor (EGFR) inhibitor. All subjects were treated with lapatinib 1,500 mg daily. Primary endpoints were response rate (arm A) and progression-free survival (PFS; arm B). The biologic effects of lapatinib on tumor growth and survival pathways were assessed in paired tumor biopsies obtained before and after therapy.
  
  
  RESULTS
  Forty-five patients were enrolled, 27 in arm A and 18 in arm B. Diarrhea was the most frequent toxicity occurring in 49% of patients. Seven patients experienced related grade 3 toxicity (3 fatigue, 2 hyponatremia, 1 vomiting, and 1 diarrhea). In an intent-to-treat analysis, no complete or partial responses were observed, and stable disease was the best response observed in 41% of arm A (median duration, 50 days, range, 34-159) and 17% of arm B subjects (median, 163 days, range, 135-195). Median PFS was 52 days in both arms. Median OS was 288 (95% CI, 62-374) and 155 (95% CI, 75-242) days for arms A and B, respectively. Correlative analyses revealed an absence of EGFR inhibition in tumor tissue.
  
  
  CONCLUSIONS
  Lapatinib as a single agent in recurrent/metastatic SCCHN, although well tolerated, appears to be inactive in either EGFR inhibitor naive or refractory subjects.
authors.affiliation: Section of Hematology/Oncology, Department of Medicine, The University of Chicago Medical Center, Chicago, Illinois, USA.
authors.forename: Jonas A
authors.initials: JA
authors.lastname: de Souza
authors.forename: Darren W
authors.initials: DW
authors.lastname: Davis
authors.forename: Yujian
authors.initials: Y
authors.lastname: Zhang
authors.forename: Arun
authors.initials: A
authors.lastname: Khattri
authors.forename: Tanguy Y
authors.initials: TY
authors.lastname: Seiwert
authors.forename: Serdal
authors.initials: S
authors.lastname: Aktolga
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Wong
authors.forename: Mark F
authors.initials: MF
authors.lastname: Kozloff
authors.forename: Sreenivasa
authors.initials: S
authors.lastname: Nattam
authors.forename: Mark W
authors.initials: MW
authors.lastname: Lingen
authors.forename: Rangesh
authors.initials: R
authors.lastname: Kunnavakkam
authors.forename: Kerstin M
authors.initials: KM
authors.lastname: Stenson
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Blair
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Bozeman
authors.forename: Janet E
authors.initials: JE
authors.lastname: Dancey
authors.forename: Everett E
authors.initials: EE
authors.lastname: Vokes
authors.forename: Ezra E W
authors.initials: EE
authors.lastname: Cohen
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy*; D006801:Humans; D000077341:Lapatinib; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D011799:Quinazolines / Q000008:administration & dosage* / Q000009:adverse effects* / Q000627:therapeutic use; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D000077341:Lapatinib; D066246:ErbB Receptors