title: Phase II study of lapatinib in recurrent or metastatic epidermal growth factor receptor and/or erbB2 expressing adenoid cystic carcinoma and non adenoid cystic carcinoma malignant tumors of the salivary glands.
abstract: OBJECTIVE
  Expression of erbB2 and/or epidermal growth factor receptor (EGFR) is associated with biologic aggressiveness and poor prognosis in malignant salivary gland tumors (MSGTs). This phase II study was conducted to determine the antitumor activity of lapatinib, a dual inhibitor of EGFR and erbB2 tyrosine kinase activity, in MSGTs.
  
  
  METHODS
  Patients with progressive, recurrent, or metastatic adenoid cystic carcinoma (ACC) immunohistochemically expressing at least 1+ EGFR and/or 2+ erbB2 were treated with lapatinib 1,500 mg daily, in a two-stage cohort. Patients with non-ACC MSGTs were treated as a separate single-stage cohort.
  
  
  RESULTS
  Of 62 patients screened, 29 of 33 (88%) ACC and 28 of 29 (97%) non-ACC patients expressed EGFR and/or erbB2. Forty patients with progressive disease were enrolled onto the study. Among 19 assessable ACC patients, there were no objective responses, 15 patients (79%) had stable disease (SD), nine patients (47%) had SD > or = 6 months, and four patients (21%) had progressive disease (PD). For 17 assessable non-ACC patients, there were no objective responses, eight patients (47%) had SD, four patients (24%) had SD > or = 6 months, and nine patients (53%) had PD. The most frequent adverse events were grade 1 to 2 diarrhea, fatigue, and rash. Eight paired tumor biopsies for correlative studies were procured; results did not correlate with clinical outcome.
  
  
  CONCLUSIONS
  Although no responses were observed, lapatinib was well tolerated, with prolonged tumor stabilization of > or = 6 months in 36% (95% CI, 21% to 54%) of assessable patients. The antitumor effects of lapatinib in MGSTs appear mainly cytostatic, hence evaluation of other molecular targeted agents, or combinations with lapatinib, may be considered. Continued efforts should be made to gain better understanding into the biology of this heterogeneous group of malignancies.
authors.affiliation: Princess Margaret Hospital Phase II Consortium, Toronto, Ontario, Canada.
authors.forename: Mark
authors.initials: M
authors.lastname: Agulnik
authors.forename: Ezra W E
authors.initials: EW
authors.lastname: Cohen
authors.forename: Roger B
authors.initials: RB
authors.lastname: Cohen
authors.forename: Eric X
authors.initials: EX
authors.lastname: Chen
authors.forename: Everett E
authors.initials: EE
authors.lastname: Vokes
authors.forename: Sebastien J
authors.initials: SJ
authors.lastname: Hotte
authors.forename: Eric
authors.initials: E
authors.lastname: Winquist
authors.forename: Scott
authors.initials: S
authors.lastname: Laurie
authors.forename: D Neil
authors.initials: DN
authors.lastname: Hayes
authors.forename: Janet E
authors.initials: JE
authors.lastname: Dancey
authors.forename: Shirley
authors.initials: S
authors.lastname: Brown
authors.forename: Gregory R
authors.initials: GR
authors.lastname: Pond
authors.forename: Ian
authors.initials: I
authors.lastname: Lorimer
authors.forename: Manijeh
authors.initials: M
authors.lastname: Daneshmand
authors.forename: James
authors.initials: J
authors.lastname: Ho
authors.forename: Ming-Sound
authors.initials: MS
authors.lastname: Tsao
authors.forename: Lillian L
authors.initials: LL
authors.lastname: Siu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D003528:Carcinoma, Adenoid Cystic / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000556:secondary*; D018572:Disease-Free Survival; D004815:Epidermal Growth Factor / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000077341:Lapatinib; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011799:Quinazolines / Q000627:therapeutic use*; D012468:Salivary Gland Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; C413364:ERBIN protein, human; D011799:Quinazolines; D000077341:Lapatinib; D004815:Epidermal Growth Factor; D011505:Protein-Tyrosine Kinases