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
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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DOI：
10.1007/s10637-011-9650-4
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发表时间：
2012-06-01
影响因子：
3.4
通讯作者：
Oza, Amit M.
中科院分区：
文献类型：
--
作者：
Mackay, Helen J.;Au, Heather J.;Oza, Amit M.
目的Src激酶家族可能在胃癌的发生发展中起一定作用。我们评估了Saracatinib（一种口服苯胺喹唑酮，靶向Src激酶的非受体酪氨酸激酶抑制剂）在转移性或局部晚期胃癌患者中的活性和安全性。方法接受≥ 16周的合格患者。结果10例胃癌和11例胃食管交界处腺癌患者接受了中位2个周期（范围1-10个周期）的治疗。17例患者可评价缓解。未观察到客观缓解。1例患者出现长期疾病稳定（pSD）。3例患者发生SD，13例发生疾病进展。中位总生存期为7.8个月（95% CI：3.9-12.2个月），中位至进展时间为1.8个月（95% CI：1.51.9个月）。可能与saracatinib相关的3级事件包括：疲乏（2例患者）、缺氧（2例）、贫血（3例）和淋巴细胞减少症（2例）。结论Saracatinib单药治疗晚期胃腺癌疗效不佳，值得进一步研究。胃癌的进一步发展需要合理的药物组合或鉴定对Src抑制敏感的肿瘤表型。
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 = 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: 1.51.9 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.