Department of Urology, Peking University First Hospital, Institute of Urology, Peking University, National Urological Cancer Center, Beijing 100034, China.
Chin Med J (Engl). 2011 Sep;124(18):2920-4.
The tyrosine kinase inhibitors (TKIs) sunitinib, the first targeted agent for the first line treatment of metastatic renal cell carcinoma (RCC), targets the vascular endothelial growth factor (VEGF) pathway. The objective of this study was to investigate the efficacy and safety of sunitinib in treating metastatic clear-cell RCC and to confirm if hypertension is an effective predictive factor.
A total of 36 patients with metastatic RCC were enrolled between June 2008 and December 2010. Among them 29 cases were first line therapy and 7 cases were in progression on first-line cytokine or sorafinib therapy. The pathology of all patients was confirmed predominant in clear cell type. Sunitinib mono-therapy was administered in repeated 6-week cycles of daily oral therapy for 4 weeks, followed by 2 weeks off in 34 patients; and 3 patients were administered with 37.5 mg/d continuously until disease progression or unacceptable toxicities occurred. Overall response rate and safety were evaluated. We divided patients into Group A and Group B according to the blood pressure level.
The median follow-up was 15 months (10 cycles, range 1.5 - 30.0 months (1 - 20 cycles)). Ten patients (29.4%) achieved partial responses (PR); 23 patients (67.6%) demonstrated stable disease (SD) lasting ≥ 2 cycles. Seventeen patients (50%) developed progressive disease (PD) during follow-up. The median progression-free survival (PFS) was 15 months (range 3.0 - 28.5) months. A total of 9 patients died; the overall survival has not been reached; the median survival time of the deceased patients was 13 months (range 7 - 24) months. The most common adverse events were hand-foot syndrome (77.8%), thrombocytopenia (75.0%), hypertension (61.1%) and diarrhea (46.0%). Most adverse events were reversible by treatment interruption. Twenty-two patients (61.1%) developed hypertension; and hypertension was associated with a long time to disease progression and long overall survival (P = 0.004, 0.000, respectively).
The results of this study demonstrate the efficacy and manageable adverse event profile of sunitinib as a single agent in first- or second-line therapy for patients with metastatic clear cell RCC. Further, sunitinib-associated hypertension may be a strong predictive marker for treatment efficacy in metastatic RCC.
酪氨酸激酶抑制剂（TKIs）舒尼替尼是转移性肾细胞癌（RCC）一线治疗的第一种靶向药物，其作用靶点为血管内皮生长因子（VEGF）通路。本研究旨在评估舒尼替尼治疗转移性透明细胞 RCC 的疗效和安全性，并确认高血压是否为有效的预测因素。
2008 年 6 月至 2010 年 12 月期间，共纳入 36 例转移性 RCC 患者。其中 29 例为一线治疗，7 例为一线细胞因子或索拉非尼治疗进展。所有患者的病理均证实为透明细胞为主。34 例患者给予舒尼替尼单药治疗，每日口服重复 6 周周期，4 周治疗，2 周停药；3 例患者给予 37.5mg/d 连续治疗，直至疾病进展或不可耐受的毒性发生。评估总缓解率和安全性。根据血压水平将患者分为 A 组和 B 组。
中位随访时间为 15 个月（10 个周期，范围 1.5-30.0 个月（1-20 个周期））。10 例患者（29.4%）获得部分缓解（PR）；23 例患者（67.6%）的疾病稳定（SD）持续≥2 个周期。17 例患者（50%）在随访期间发生疾病进展（PD）。中位无进展生存期（PFS）为 15 个月（范围 3.0-28.5）个月。共有 9 例患者死亡；总生存期尚未达到；死亡患者的中位生存时间为 13 个月（范围 7-24）个月。最常见的不良反应为手足综合征（77.8%）、血小板减少症（75.0%）、高血压（61.1%）和腹泻（46.0%）。大多数不良反应通过中断治疗即可逆转。22 例患者（61.1%）发生高血压；高血压与疾病进展时间延长和总生存期延长相关（P=0.004、0.000，分别）。
本研究结果表明，舒尼替尼作为转移性透明细胞 RCC 一线或二线治疗的单一药物，具有疗效和可管理的不良反应谱。此外，舒尼替尼相关的高血压可能是转移性 RCC 治疗疗效的一个强有力的预测标志物。
