Motzer Robert J, Rini Brian I, Bukowski Ronald M, Curti Brendan D, George Daniel J, Hudes Gary R, Redman Bruce G, Margolin Kim A, Merchan Jaime R, Wilding George, Ginsberg Michelle S, Bacik Jennifer, Kim Sindy T, Baum Charles M, Michaelson M Dror
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
JAMA. 2006 Jun 7;295(21):2516-24. doi: 10.1001/jama.295.21.2516.
Current treatment options for metastatic renal cell carcinoma (RCC) are limited and there is a need to identify novel and effective therapies. Sunitinib malate is an oral multitargeted tyrosine kinase inhibitor, which has shown activity in an initial study of cytokine-refractory metastatic RCC patients.
To confirm the antitumor efficacy of sunitinib as second-line treatment in patients with metastatic clear-cell RCC, the predominant cell type of this malignancy.
DESIGN, SETTING, AND PATIENTS: Open-label, single-arm, multicenter clinical trial. Patients were enrolled between February and November 2004, with follow-up continuing until disease progression, unacceptable toxicity, or withdrawal of consent. The reported data apply through August 2005. Patients (N = 106) had metastatic clear-cell RCC, which had progressed despite previous cytokine therapy.
Repeated 6-week cycles of sunitinib, 50 mg per day given orally for 4 consecutive weeks followed by 2 weeks off per treatment cycle.
Assessment of clinical response, degree of tumor regression on imaging studies using the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines. Primary end point was overall objective response rate (complete plus partial). Secondary end points were progression-free survival and safety. Response was evaluated by independent third-party core imaging laboratory and by treating physicians (investigator assessment).
All 106 patients received sunitinib and were included in the intent-to-treat population for safety analyses. Of these, 105 patients were evaluable for efficacy analyses. The objective response rate according to an independent third-party assessment resulted in 36 patients with partial response (34%; 95% confidence interval, 25%-44%), and a median progression-free survival of 8.3 months (95% confidence interval, 7.8-14.5 months). The most common adverse events experienced by patients were fatigue in 30 (28%) and diarrhea 21 (20%). Neutropenia, elevation of lipase, and anemia were the most common laboratory abnormalities observed in 45 (42%), 30 (28%), and 27 (26%) patients, respectively.
The results of this trial demonstrate the efficacy and manageable adverse-event profile of sunitinib as a single agent in second-line therapy for patients with cytokine-refractory metastatic clear-cell RCC.
clinicaltrials.gov Identifier: NCT00077974.
转移性肾细胞癌（RCC）目前的治疗选择有限，因此需要确定新的有效治疗方法。苹果酸舒尼替尼是一种口服多靶点酪氨酸激酶抑制剂，在细胞因子难治性转移性RCC患者的初步研究中已显示出活性。
确认舒尼替尼作为转移性透明细胞RCC（该恶性肿瘤的主要细胞类型）患者二线治疗的抗肿瘤疗效。
设计、地点和患者：开放标签、单臂、多中心临床试验。患者于2004年2月至11月入组，随访持续至疾病进展、出现不可接受的毒性或患者撤回同意书。报告的数据截至2005年8月。患者（N = 106）患有转移性透明细胞RCC，尽管先前接受过细胞因子治疗，但病情仍有进展。
舒尼替尼重复进行6周疗程，每天口服50 mg，连续服用4周，然后每个治疗周期停药2周。
根据实体瘤疗效评价标准（RECIST）指南评估临床反应、影像学研究中的肿瘤消退程度。主要终点是总体客观缓解率（完全缓解加部分缓解）。次要终点是无进展生存期和安全性。反应由独立的第三方核心影像实验室和治疗医生（研究者评估）进行评估。
所有106例患者均接受了舒尼替尼治疗，并被纳入安全性分析的意向性治疗人群。其中，105例患者可进行疗效分析。根据独立第三方评估，客观缓解率为36例部分缓解（34%；95%置信区间，25%-44%），无进展生存期的中位数为8.3个月（95%置信区间，7.8-14.5个月）。患者最常见的不良事件为疲劳（30例，28%）和腹泻（21例，20%）。中性粒细胞减少、脂肪酶升高和贫血是分别在45例（42%）、30例（28%）和27例（26%）患者中观察到的最常见实验室异常。
该试验结果表明，舒尼替尼作为单一药物用于细胞因子难治性转移性透明细胞RCC患者的二线治疗具有疗效且不良事件可控。
clinicaltrials.gov标识符：NCT00077974。
