Department of Medical Oncology, Sir Charles Gairdner Hospital, Nedlands, Australia.
J Thorac Oncol. 2012 Sep;7(9):1449-56. doi: 10.1097/JTO.0b013e31825f22ee.
There is no accepted second-line therapy for patients with advanced malignant pleural mesothelioma (MPM), whose disease has progressed after first-line chemotherapy. The multitargeted tyrosine kinase inhibitor sunitinib malate targets several pathways overexpressed in mesothelioma. This phase II study assessed objective response to sunitinib and correlative biomarkers in patients with progressive pretreated MPM.
Eligible patients had confirmed MPM, radiological progression after chemotherapy, Eastern Cooperative Oncology Group performance status 0 to 1, and measurable disease. Patients received oral sunitinib 50 mg daily for 28 of every 42 days. The primary endpoint was objective radiological response. Patients without prior pleurodesis had fluorodeoxyglucose positron emission tomographic response assessed by total glycolytic volume criteria. Correlative biomarkers included serum mesothelin, vascular endothelial growth factor (VEGF)-A, VEGF-C, interleukin-8, sVEGFR-2, sVEGFR-3, and s-kit.
Fifty-three patients received sunitinib between July 2006 and December 2009; 51 were assessable for response. Patients received a median of two cycles (range, 1-12); 40% required dose reduction. Fatigue was the most prominent toxicity. Six patients (12%) had a confirmed radiological partial response, 34 (65%) had stable disease, and 11 (22%) had progressive disease as best response. Six of 20 patients had a decrease in fluorodeoxyglucose positron emission tomographic total glycolytic volume of 15% or more. Median overall survival was 6.1 months, and median time to progression was 3.5 months. Correlative biomarkers did not predict treatment response.
Sunitinib has activity in a subset of patients with pretreated MPM. Consideration should be given to different treatment schedules and examination of other biomarkers for further study of sunitinib in MPM.
对于一线化疗后疾病进展的晚期恶性胸膜间皮瘤（MPM）患者，尚无被接受的二线治疗方法。多靶点酪氨酸激酶抑制剂苹果酸舒尼替尼针对间皮瘤中过度表达的多个途径。这项评估索坦治疗进展性预处理 MPM 患者的客观反应和相关生物标志物的 II 期研究。
合格的患者有明确的 MPM，化疗后影像学进展，东部合作肿瘤组表现状态 0 到 1，和可测量的疾病。患者接受口服舒尼替尼 50 毫克，每天一次，每 42 天服用 28 天。主要终点是客观的影像学反应。没有先前行胸膜固定术的患者，根据总糖酵解体积标准评估氟脱氧葡萄糖正电子发射断层扫描的反应。相关的生物标志物包括血清间皮素、血管内皮生长因子（VEGF）-A、VEGF-C、白细胞介素-8、sVEGFR-2、sVEGFR-3 和 s-kit。
53 例患者于 2006 年 7 月至 2009 年 12 月接受舒尼替尼治疗；51 例患者可评估反应。患者接受中位数为两个周期（范围，1-12）；40%需要剂量减少。疲劳是最突出的毒性。6 例（12%）有确认的影像学部分缓解，34 例（65%）有稳定的疾病，11 例（22%）有最佳反应的疾病进展。20 例患者中有 6 例（30%）氟脱氧葡萄糖正电子发射断层扫描的总糖酵解体积减少 15%或更多。中位总生存期为 6.1 个月，中位无进展生存期为 3.5 个月。相关生物标志物不能预测治疗反应。
舒尼替尼在预处理 MPM 的患者亚群中具有活性。应考虑不同的治疗方案，并进一步研究舒尼替尼在 MPM 中的其他生物标志物。
