Socinski Mark A
Multidisciplinary Thoracic Oncology Program, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599-7305, USA.
J Thorac Oncol. 2008 Jun;3(6 Suppl 2):S119-23. doi: 10.1097/JTO.0b013e318174e9be.
Sunitinib, a small molecule, is a multitargeted receptor kinase inhibitor which targets the vascular endothelial growth factor receptor and platelet-derived growth factor receptor as well as several others. Initially approved for the treatment of renal cell carcinoma as well as imatinib-resistant gastrointestinal stromal tumors, the activity of sunitinib has been explored in several other solid tumors including non-small cell lung cancer (NSCLC). An initial phase II trial in 63 previously treated NSCLC patients using a dose of 50 mg daily 4 of 6 weeks showed a response rate of 11.1% and a stable disease rate of 26.8%. The median time to disease progression and overall survival was 12.0 and 23.4 weeks, respectively. The principal toxicities included fatigue, pain, myalgias, nausea/vomiting, and hypertension. Three hemorrhagic deaths were reported (two pulmonary and one central nervous system). After this trial was completed, a subsequent sequential cohort of 47 previously treated NSCLC patients were treated on a continuous dosing schedule of sunitinib at 37.5 mg daily. A response rate of 2.1% was reported with a stable disease rate of 19.X%. The median time to progression was 12.3 weeks with a median survival time of 38.1 week. Toxicities were, in general, less frequent and similar to those noted in the initial trial. Sunitinib is currently being evaluated in combination with a number of standard regimens commonly used in NSCLC as well as a maintenance drug after first-line platinum-based treatment of advanced NSCLC. Results of these trials are eagerly awaited and will help define the role of sunitinib in the therapeutic approach to NSCLC.
舒尼替尼是一种小分子多靶点受体激酶抑制剂，可作用于血管内皮生长因子受体、血小板衍生生长因子受体以及其他多种靶点。它最初被批准用于治疗肾细胞癌以及对伊马替尼耐药的胃肠道间质瘤，其在包括非小细胞肺癌（NSCLC）在内的其他多种实体瘤中的活性也已得到探索。一项针对63例先前接受过治疗的NSCLC患者的II期初始试验，采用每日50毫克、每6周服用4周的剂量，结果显示缓解率为11.1%，疾病稳定率为26.8%。疾病进展的中位时间和总生存期分别为12.0周和23.4周。主要毒性包括疲劳、疼痛、肌痛、恶心/呕吐和高血压。报告了3例出血性死亡（2例肺部出血和1例中枢神经系统出血）。该试验完成后，后续有47例先前接受过治疗的NSCLC患者按照舒尼替尼每日37.5毫克的持续给药方案进行治疗。报告的缓解率为2.1%，疾病稳定率为19.X%。进展的中位时间为12.3周，中位生存时间为38.1周。总体而言，毒性的发生频率较低，且与初始试验中观察到的毒性相似。目前正在评估舒尼替尼与NSCLC常用的多种标准方案联合使用的效果，以及在晚期NSCLC一线铂类治疗后作为维持药物的效果。人们急切期待这些试验的结果，它们将有助于明确舒尼替尼在NSCLC治疗方法中的作用。
