University Hospitals Seidman Cancer Center and.
Oncologist. 2013;18(10):1091-2. doi: 10.1634/theoncologist.2013-0255. Epub 2013 Sep 26.
Src, EphA2, and platelet-derived growth factor receptors α and β are dysregulated in pancreatic ductal adenocarcinoma (PDAC).
Dasatinib is an oral multitarget tyrosine kinase inhibitor that targets BCR-ABL, c-Src, c-KIT, platelet-derived growth factor receptor β, and EphA2. We conducted a phase II, single-arm study of dasatinib as first-line therapy in patients with metastatic PDAC.
Dasatinib (100 mg twice a day, later reduced to 70 mg twice a day because of toxicities) was orally administered continuously on a 28-day cycle. The primary endpoint was overall survival (OS). Response was measured using the Response Evaluation Criteria in Solid Tumors. Circulating tumor cells (CTCs) were also collected.
Fifty-one patients enrolled in this study. The median OS was 4.7 months (95% confidence interval [CI]: 2.8-6.9 months). Median progression-free survival was 2.1 months (95% CI: 1.6-3.2 months). In 34 evaluable patients, the best response achieved was stable disease in 10 patients (29.4%). One patient had stable disease while on treatment for 20 months. The most common nonhematologic toxicities were fatigue and nausea. Edema and pleural effusions occurred in 29% and 6% of patients, respectively. The number of CTCs did not correlate with survival.
Single-agent dasatinib does not have clinical activity in metastatic PDAC.
Src、EphA2 以及血小板衍生生长因子受体 α 和 β 在胰腺导管腺癌（PDAC）中失调。
达沙替尼是一种口服多靶点酪氨酸激酶抑制剂，可靶向 BCR-ABL、c-Src、c-KIT、血小板衍生生长因子受体 β 和 EphA2。我们进行了一项达沙替尼作为转移性 PDAC 一线治疗的 II 期、单臂研究。
达沙替尼（100 mg，每日两次，因毒性反应后减至 70 mg，每日两次）连续 28 天周期口服给药。主要终点是总生存期（OS）。使用实体瘤反应评估标准测量反应。还收集了循环肿瘤细胞（CTC）。
51 例患者入组本研究。中位 OS 为 4.7 个月（95%置信区间 [CI]：2.8-6.9 个月）。中位无进展生存期为 2.1 个月（95%CI：1.6-3.2 个月）。在 34 例可评估患者中，最佳缓解为 10 例患者（29.4%）疾病稳定。1 例患者在治疗 20 个月时疾病稳定。最常见的非血液学毒性是疲劳和恶心。水肿和胸腔积液分别发生在 29%和 6%的患者中。CTC 数量与生存无关。
单药达沙替尼在转移性 PDAC 中无临床活性。
