title: Southwest Oncology Group study S0413: a phase II trial of lapatinib (GW572016) as first-line therapy in patients with advanced or metastatic gastric cancer.
abstract: BACKGROUND
  Lapatinib (GW572016) is a dual tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2/ErbB2), which are reported as overexpressed in 15%-45% of gastric cancers, making them potential targets.
  
  
  METHODS
  The primary objective of this study was to assess response rate. Secondary objectives included overall survival (OS), toxicity, and the relationship of EGFR, ErbB2, and markers of angiogenesis with clinical outcome. Lapatinib was administered to chemonaive metastatic gastric cancer patients at a dose of 1500 mg orally daily for 28 days.
  
  
  RESULTS
  The study enrolled 47 patients from February 2005 until May 2006. Four patients (9%) had a confirmed partial response (PR), 1 (2%) had an unconfirmed PR, and 10 (23%) had stable disease. Median (95% confidence interval) time to treatment failure was 1.9 (1.6-3.1) months and OS was 4.8 (3.2-7.4) months. Significant adverse events: one grade 4 cardiac ischemia/infarction, one grade 4 fatigue, and one grade 4 emesis. One treatment-related death was due to central nervous system ischemia. An exploratory analysis of markers revealed gene expression of HER2, interleukin (IL)-8 and genomic polymorphisms IL-8, and vascular endothelial growth factor correlated with OS.
  
  
  CONCLUSIONS
  Lapatinib is well tolerated, with modest single-agent activity in advanced/metastatic gastric cancer patients. Potential molecular correlatives were identified which warrant further validation.
authors.affiliation: Division of Medical Oncology, University of Southern California, Los Angeles. Electronic address: iqbal@usc.edu.
authors.forename: S
authors.initials: S
authors.lastname: Iqbal
authors.affiliation: Southwest Oncology Group Statistical Center, Seattle.
authors.forename: B
authors.initials: B
authors.lastname: Goldman
authors.affiliation: Department of Pathology, University of Cincinnati, Cincinnati.
authors.forename: C M
authors.initials: CM
authors.lastname: Fenoglio-Preiser
authors.affiliation: Division of Medical Oncology, University of Southern California, Los Angeles.
authors.forename: H J
authors.initials: HJ
authors.lastname: Lenz
authors.affiliation: Division of Medical Oncology, University of Southern California, Los Angeles.
authors.forename: W
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Response Genetics, Inc., Los Angeles.
authors.forename: K D
authors.initials: KD
authors.lastname: Danenberg
authors.affiliation: Department of Medical Oncology, City of Hope National Medical Center, Duarte, USA.
authors.forename: S I
authors.initials: SI
authors.lastname: Shibata
authors.affiliation: Department of Medical Oncology, British Columbia Cancer Agency, University of British Columbia, Vancouver, Canada.
authors.forename: C D
authors.initials: CD
authors.lastname: Blanke
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000556:secondary; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D053208:Kaplan-Meier Estimate; D000077341:Lapatinib; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011799:Quinazolines / Q000627:therapeutic use*; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D011799:Quinazolines; D000077341:Lapatinib