Jay Raman, McKay R R, Werner L, Atkins M B, Van Allen E M, Olivier K M, Song J, Signoretti S, McDermott D F, Choueiri T K
Urol Oncol. 2017 Mar;35(3):117-118. doi: 10.1016/j.urolonc.2016.12.023. Epub 2017 Feb 1.
Sarcomatoid renal cell carcinoma (RCC) is associated with an aggressive biology and a poor prognosis. Poor-risk RCC is defined by clinical prognostic factors and demonstrates similarly aggressive behavior. No standard treatment exists for patients with sarcomatoid RCC, and treatment options for patients with poor-risk disease are of limited benefit. The objective of this study was to investigate the efficacy of antiangiogenic therapy in combination with cytotoxic chemotherapy in clinically aggressive RCC.
This was a phase 2, single-arm trial of sunitinib and gemcitabine in patients with sarcomatoid or poor-risk RCC. The primary end point was the objective response rate (ORR). Secondary end points included the time to progression (TTP), overall survival (OS), safety, and biomarker correlatives.
Overall, 39 patients had sarcomatoid RCC, and 33 had poor-risk RCC. The ORR was 26% for patients with sarcomatoid RCC and 24% for patients with poor-risk RCC. The median TTP and OS for patients with sarcomatoid RCC were 5 and 10 months, respectively. For patients with poor-risk disease, the median TTP and OS were 5.5 and 15 months, respectively. Patients whose tumors had>10% sarcomatoid histology had a higher clinical benefit rate (ORR plus stable disease) than those with≤10% sarcomatoid histology (P = 0.04). The most common grade 3 or higher treatment-related adverse events included neutropenia (n = 20), anemia (n = 10), and fatigue (n = 7).
These results suggest that antiangiogenic therapy and cytotoxic chemotherapy are an active and well-tolerated combination for patients with aggressive RCC. The combination may be more efficacious than either therapy alone and is currently under further investigation.
肉瘤样肾细胞癌（RCC）具有侵袭性生物学行为且预后较差。高危RCC由临床预后因素定义，并表现出类似的侵袭性行为。对于肉瘤样RCC患者，尚无标准治疗方案，高危疾病患者的治疗选择获益有限。本研究的目的是调查抗血管生成疗法联合细胞毒性化疗在临床侵袭性RCC中的疗效。
这是一项关于舒尼替尼和吉西他滨用于肉瘤样或高危RCC患者的2期单臂试验。主要终点是客观缓解率（ORR）。次要终点包括疾病进展时间（TTP）、总生存期（OS）、安全性和生物标志物相关性。
总体而言，39例患者患有肉瘤样RCC，33例患有高危RCC。肉瘤样RCC患者的ORR为26%，高危RCC患者的ORR为24%。肉瘤样RCC患者的中位TTP和OS分别为5个月和10个月。对于高危疾病患者，中位TTP和OS分别为5.5个月和15个月。肿瘤具有>10%肉瘤样组织学特征的患者的临床获益率（ORR加疾病稳定）高于肉瘤样组织学特征≤10%的患者（P = 0.04）。最常见的3级或更高等级的治疗相关不良事件包括中性粒细胞减少（n = 20）、贫血（n = 10）和疲劳（n = 7）。
这些结果表明，抗血管生成疗法和细胞毒性化疗对于侵袭性RCC患者是一种有效的且耐受性良好的联合治疗方案。该联合治疗可能比单独使用任何一种疗法更有效，目前正在进一步研究中。
