title: HER2/neu may not be an interesting target in biliary cancers: results of an early phase II study with lapatinib.
abstract: OBJECTIVE
  Biliary cancers (BCs) respond poorly to chemotherapy. Lapatinib is a dual inhibitor of epidermal growth factor receptor (EGFR) and HER2/neu, both implicated in cholangiocarcinogenesis. This trial was designed to determine the safety and efficacy of lapatinib in BC.
  
  
  METHODS
  A Fleming phase II design with a single stage of 25 patients was used. The dose of lapatinib was 1,500 mg/day administered orally in 28-day cycles. Tumor and blood specimens were analyzed for expression of HER2/neu and EGFR.
  
  
  RESULTS
  Nine patients with BC enrolled in this study. The study was terminated early because of futility. The most common toxicities were nausea and fatigue (78%) and diarrhea (67%). No responses were observed. Of 8 evaluable patients, 4 (50%) had stable disease. Median progression-free survival was 2.6 months (95% CI 1.6-4.4) and median overall survival was 5.1 months (95% CI 2.0-16.5). No somatic mutations in EGFR (exons 18-21) or HER2/neu were found. We did not find evidence of HER2 overexpression.
  
  
  CONCLUSIONS
  Lapatinib is well tolerated but failed to show activity as a single agent in treating patients with BC. Despite the small patient population, our study is consistent with previous findings, suggesting that targeting HER2/neu does not appear to be an effective therapy for BC.
authors.affiliation: The Ohio State University Comprehensive Cancer Center, James Cancer Hospital and Solove Research Institute, Columbus, Ohio, USA.
authors.forename: Joshua
authors.initials: J
authors.lastname: Peck
authors.forename: Lai
authors.initials: L
authors.lastname: Wei
authors.forename: Mark
authors.initials: M
authors.lastname: Zalupski
authors.forename: Bert
authors.initials: B
authors.lastname: O'Neil
authors.forename: Miguel
authors.initials: M
authors.lastname: Villalona Calero
authors.forename: Tanios
authors.initials: T
authors.lastname: Bekaii-Saab
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001661:Biliary Tract Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000401:mortality; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics; D005260:Female; D006801:Humans; D000077341:Lapatinib; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009362:Neoplasm Metastasis; D011379:Prognosis; D011799:Quinazolines / Q000627:therapeutic use*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015996:Survival Rate
chemical_list: D000970:Antineoplastic Agents; D066246:ErbB Receptors; D000077341:Lapatinib; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; C512478:EGFR protein, human