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
Autor: | John Wright, Elaine McWhirter, Lisa Wang, Amit M. Oza, Heather Jane Au, K. MacAlpine, Andrea Jarvi, Thierry Alcindor, Helen Mackay |
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Rok vydání: | 2011 |
Předmět: |
Adult
Male medicine.medical_specialty Esophageal Neoplasms Anemia medicine.drug_class medicine.medical_treatment Adenocarcinoma Gastroenterology Tyrosine-kinase inhibitor Stomach Neoplasms Internal medicine medicine Clinical endpoint Humans Pharmacology (medical) Benzodioxoles Neoplasm Metastasis Protein Kinase Inhibitors Aged Aged 80 and over Pharmacology Chemotherapy business.industry Cancer Middle Aged medicine.disease Surgery Clinical trial src-Family Kinases Oncology Quinazolines Female Esophagogastric Junction business Progressive disease |
Zdroj: | Investigational New Drugs. 30:1158-1163 |
ISSN: | 1573-0646 0167-6997 |
Popis: | 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. |
Databáze: | OpenAIRE |
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