Genitourinary OncologyService, Division of Solid Tumor Oncology,and the Departments of Radiology,Medicine, Memorial Sloan-Kettering Cancer Center,New York, NY, USA
J Clin Oncol. 2010 Mar 10;28(8):1373-9. doi: 10.1200/JCO.2009.25.3922. Epub 2010 Feb 8.
No standard therapy exists for metastatic urothelial cancer (UC) that has progressed after initial chemotherapy. This trial was designed to assess the efficacy and tolerability of sunitinib in patients with advanced, previously treated UC.
In this phase II trial, 77 patients received sunitinib between September 2006 and January 2009 on one of two schedules (50 mg per day for 4 weeks on and 2 weeks off [cohort A], 37.5 mg per day continuously [cohort B]), using a Simon 2 stage design in each cohort separately.
A partial response was seen in three of 45 patients (95% CI, 1% to 18%) in cohort A, and in one of 32 patients (95% CI, 0% to 16%) in cohort B. Clinical regression or stable disease was achieved in 33 of 77 patients (43%). Tumor regression lasted between 0.6 and 23.4 months with 29% of patients achieving response lasting longer than 3 months. The progression-free survival (2.4 v 2.3 months; P = .4) and overall survival (7.1 v 6.0 months; P = .4) were similar in both cohorts. There was one treatment-related death, and 47 patients (33 cohort A, 24 cohort B) experienced grade 3 or 4 toxicity.
Sunitinib did not achieve the predetermined threshold of >or= 20% activity defined by Response Evaluation Criteria in Solid Tumors. However, antitumor responses were observed, identifying the vascular endothelial growth factor axis as a viable pathway for UC treatment. The reported clinical benefit in previously treated patients warrants further investigation in a disease for which there is no US Food and Drug Administration-approved treatment.
初始化疗后进展的转移性尿路上皮癌（UC）尚无标准治疗方法。本试验旨在评估舒尼替尼在晚期、既往治疗过的 UC 患者中的疗效和耐受性。
在这项 2 期试验中，77 例患者于 2006 年 9 月至 2009 年 1 月期间分别接受了两种方案的舒尼替尼治疗（方案 A：50mg/d，连用 4 周，停药 2 周；方案 B：37.5mg/d，持续用药），每个方案分别采用 Simon 两阶段设计。
方案 A 中 45 例患者中有 3 例（95%CI，1%18%）出现部分缓解，方案 B 中 32 例患者中有 1 例（95%CI，0%16%）出现部分缓解。77 例患者中有 33 例（43%）出现临床退缩或疾病稳定。肿瘤缓解持续时间为 0.6~23.4 个月，29%的患者缓解持续时间超过 3 个月。两组的无进展生存期（2.4 个月比 2.3 个月；P=0.4）和总生存期（7.1 个月比 6.0 个月；P=0.4）相似。有 1 例治疗相关死亡，47 例（方案 A 中 33 例，方案 B 中 24 例）发生 3 级或 4 级毒性。
舒尼替尼未达到实体瘤反应评价标准（RECIST）定义的>或=20%的预定活性阈值。然而，观察到了抗肿瘤反应，表明血管内皮生长因子轴是 UC 治疗的可行途径。在没有美国食品和药物管理局批准的治疗方法的情况下，对于这种疾病，报告的临床获益值得进一步研究。
