title: A phase II trial of the Src kinase inhibitor saracatinib (AZD0530) in patients with metastatic or locally advanced gastric or gastro esophageal junction (GEJ) adenocarcinoma: a trial of the PMH phase II consortium.
abstract: OBJECTIVE
  The Src family of kinases may play a role in the development and progression of gastric cancer. We evaluated the activity and safety of saracatinib an oral, anilinoquinazolone, non-receptor tyrosine kinase inhibitor targeting Src kinases, in patients with metastatic or locally advanced gastric carcinoma.
  
  
  METHODS
  Eligible patients who had received ≤1 prior line of chemotherapy for metastatic disease received saracatinib 175 mg/day of a 28 day cycle until progression. The primary endpoint was the objective response and/or prolonged stable disease rate (pSD ≥ 16 weeks).
  
  
  RESULTS
  Ten patients with gastric carcinoma and 11 with adenocarcinoma of the gastroesophageal junction received a median of 2 cycles (range 1-10 cycles) of treatment per patient. 17 patients were evaluable for response. No objective response was seen. One patient experienced prolonged Stable disease (pSD). Three patients had SD and 13 progressive disease. Median overall survival was 7.8 months (95% CI, 3.9-12.2 months) and median time to progression was 1.8 months (95% CI: 1.5-1.9 months). Grade 3 events possibly related to saracatinib included: fatigue (2 patients), hypoxia (2) anemia (3) and lymphopenia (2).
  
  
  CONCLUSIONS
  Saracatinib has insufficient activity as a single agent in patients with advanced gastric adenocarcinoma to warrant further investigation. Further development in gastric cancer would require rational drug combinations or identification of a tumor phenotype sensitive to Src inhibition.
authors.affiliation: Department of Medical Oncology, Princess Margaret Hospital, University of Toronto, Ontario, Canada. helen.mackay@uhn.on.ca
authors.forename: Helen J
authors.initials: HJ
authors.lastname: Mackay
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Au
authors.forename: Elaine
authors.initials: E
authors.lastname: McWhirter
authors.forename: Thierry
authors.initials: T
authors.lastname: Alcindor
authors.forename: Andrea
authors.initials: A
authors.lastname: Jarvi
authors.forename: Katrina
authors.initials: K
authors.lastname: MacAlpine
authors.forename: Lisa
authors.initials: L
authors.lastname: Wang
authors.forename: John J
authors.initials: JJ
authors.lastname: Wright
authors.forename: Amit M
authors.initials: AM
authors.lastname: Oza
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D052117:Benzodioxoles / Q000627:therapeutic use*; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004943:Esophagogastric Junction / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011799:Quinazolines / Q000627:therapeutic use*; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D019061:src-Family Kinases / Q000037:antagonists & inhibitors
chemical_list: D052117:Benzodioxoles; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; C515233:saracatinib; D019061:src-Family Kinases