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

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• 作者：Helen J. Mackay (17) helen.mackay@uhn.on.ca
  Heather J. Au (2)
  Elaine McWhirter (3)
  Thierry Alcindor (4)
  Andrea Jarvi (5)
  Katrina MacAlpine (5)
  Lisa Wang (1)
  John J. Wright (6)
  Amit M. Oza (5)
• 关键词：Gastric cancer &#8211 ; Phase II &#8211 ; Saracatinib (AZD0530) &#8211 ; Src kinase inhibitor
• 刊名：Investigational New Drugs
• 出版年：2012
• 出版时间：June 2012
• 年：2012
• 卷：30
• 期：3
• 页码：1158-1163
• 全文大小：115.8 KB
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• 作者单位：1. Department of Medical Oncology, Princess Margaret Hospital, University of Toronto, Ontario, Canada2. Cross Cancer Institute, University of Alberta, Edmonton, AB, Canada3. Juravinski Cancer Centre, Hamilton, ON, Canada4. McGill University Health Centre, Montreal, QC, Canada5. Department of Medical Oncology, Princess Margaret Hospital, Drug Development Program, University of Toronto, Ontario, Canada6. National Cancer Institute, Rockville, MD, USA7. Princess Margaret Hospital, 610 University Ave, Toronto, ON, Canada M5G 2M9
• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Oncology
  Pharmacology and Toxicology
  
• 出版者：Springer Netherlands
• ISSN：1573-0646

文摘

Purpose 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). Conclusion 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.