转移性 RCC 的新靶向治疗
还有其他一些对RCC治疗有效果的小分子酪氨酸激酶抑制剂 (TKI) 正在被研究。[162]Atkins MB, Hidalgo M, Stadler WM, et al. Randomized phase II study of multiple dose levels of CCI-779, a novel mammalian target of rapamycin kinase inhibitor, in patients with advanced refractory renal cell carcinoma. J Clin Oncol. 2004;22:909-918.http://www.ncbi.nlm.nih.gov/pubmed/14990647?tool=bestpractice.com[163]Rini BI. Vascular endothelial growth factor-targeted therapy in metastatic renal cell carcinoma. Cancer. 2009;115(10 Suppl):2306-2312.http://www.ncbi.nlm.nih.gov/pubmed/19402073?tool=bestpractice.com此外，临床试验还在继续评估酪氨酸激酶抑制剂（和/或 m-TOR 抑制剂）的用药顺序和配伍方案。[164]Bellmunt J. Future developments in renal cell carcinoma. Ann Oncol. 2009;20(Suppl 1):i13-i17.http://www.ncbi.nlm.nih.gov/pubmed/19430003?tool=bestpractice.com能否将这些新靶向治疗药物应用于实践中将取决于 与既定靶向治疗相比较的3 期数据的累积。
多韦替尼
以血管内皮生长因子和纤维母细胞生长因子为靶点的口服酪氨酸激酶抑制剂。针对既往接受过另一种血管内皮生长因子抑制剂和 m-TOR 抑制剂治疗的患者多韦替尼作为三线用药与索拉非尼进行了比较。两个治疗小组显示出相似的无进展生存期（3.6 和 3.7 个月）。且毒性相当。[165]Motzer RJ, Porta C, Vogelzang NJ, et al. Dovitinib versus sorafenib for third-line targeted treatment of patients with metastatic renal cell carcinoma: an open-label, randomised phase 3 trial. Lancet Oncol. 2014;15:286-296.http://www.ncbi.nlm.nih.gov/pubmed/24556040?tool=bestpractice.com
替肟扎尼
一种口服靶向为血管内皮生长因子的酪氨酸激酶抑制剂，作为转移性疾病的一线治疗药物与索拉非尼进行对比。尽管早期无进展生存率分析表明替肟扎尼优于索拉非尼，但两组的最终总生存率无显著差异（风险比为 1.25）。[166]Motzer RJ, Nosov D, Eisen T, et al. Tivozanib versus sorafenib as initial targeted therapy for patients with advanced renal cell carcinoma: Results from a phase III randomized, open-label, multicenter trial. J Clin Oncol. 2012;30(suppl):abstract 4501.http://meetinglibrary.asco.org/content/96560-114[167]Motzer R, Nosov D, Eisen T, et al. Tivozanib versus sorafenib as initial targeted therapy for patients with metastatic renal cell carcinoma: results from a phase III trial. J Clin Oncol. 2013;31:3791-3799.http://jco.ascopubs.org/content/31/30/3791.longhttp://www.ncbi.nlm.nih.gov/pubmed/24019545?tool=bestpractice.com两种治疗的毒性也各不相同。
他喹莫德
一种正在被评估的可改变肿瘤微环境的新型的血管生成和免疫调节药物。[168]Raymond E, Dalgleish A, Damber JE, et al. Mechanisms of action of tasquinimod on the tumour microenvironment. Cancer Chemother Pharmacol. 2014;73:1-8.http://www.ncbi.nlm.nih.gov/pubmed/24162378?tool=bestpractice.com
尼沃鲁单抗
抗程序性死亡 (PD-1) 的单克隆抗体尼沃鲁单抗在 1 期研究中表现出良好的缓解率 (29%)，现在将其与依维莫司进行对比，用于治疗已使用过包括2种血管内皮生长因子抑制剂在内的 3 种药物治疗的患者。该研究目前正在招募患者。[169]Motzer RJ, Bono P, Hudes GR, et al. A phase III comparative study of nivolumab (anti-PD-1; BMS-936558; ONO-4538) versus everolimus in patients (pts) with advanced or metastatic renal cell carcinoma (mRCC) previously treated with antiangiogenic therapy. J Clin Oncol. 2013;31(suppl):abstract TPS4592.http://meetinglibrary.asco.org/content/113341-132
新辅助/辅助靶向治疗
目前没有数据表明手术后进行辅助治疗，包括放疗、激素治疗、化疗或免疫治疗，可以提高RCC的生存率。[170]Kapoor A, Gharajeh A, Sheikh A, et al. Adjuvant and neoadjuvant small-molecule targeted therapy in high-risk renal cell carcinoma. Curr Oncol. 2009;16(Suppl 1):S60-S66.http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=19478895http://www.ncbi.nlm.nih.gov/pubmed/19478895?tool=bestpractice.com近期，靶向药物，例如酪氨酸激酶抑制是剂和贝伐单抗作为辅助和新辅助治疗的手段正在被检验。[90]Wood CG, Margulis V. Neoadjuvant (presurgical) therapy for renal cell carcinoma: a new treatment paradigm for locally advanced and metastatic disease. Cancer. 2009;115(suppl 10):2355-2360.http://www.ncbi.nlm.nih.gov/pubmed/19402066?tool=bestpractice.com[91]Bex A, van der Veldt AA, Blank C, et al. Neoadjuvant sunitinib for surgically complex advanced renal cell cancer of doubtful resectability: initial experience with downsizing to reconsider cytoreductive surgery. World J Urol. 2009;27:533-539.http://www.ncbi.nlm.nih.gov/pubmed/19145434?tool=bestpractice.com[92]Thomas AA, Rini BI, Lane BR, et al. Response of the primary tumor to neoadjuvant sunitinib in patients with advanced renal cell carcinoma. J Urol. 2009;181:518-523.http://www.ncbi.nlm.nih.gov/pubmed/19100579?tool=bestpractice.com但是，这些研究的患者数量通常较少，且很多为恢复性研究；针对这种情况的大型研究正在进行。一项目前正在美国开展的此类跨国试验为 ASSURE 试验（或 ECOG-E2805）。该研究将肾切除术后风险分级达中高或极高的患者随机分组并给于1 年的舒尼替尼、索拉非尼或安慰剂的辅助治疗效果。[170]Kapoor A, Gharajeh A, Sheikh A, et al. Adjuvant and neoadjuvant small-molecule targeted therapy in high-risk renal cell carcinoma. Curr Oncol. 2009;16(Suppl 1):S60-S66.http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=19478895http://www.ncbi.nlm.nih.gov/pubmed/19478895?tool=bestpractice.com另一项大型试验正在检验帕唑帕尼对比安慰剂的辅助治疗。[171]Rexer H. Adjuvant AUO study of renal cell carcinoma after nephrectomy: randomized, double-blind, placebo-controlled phase III study (PROTECT - AN 30/10) to investigate the effectiveness and safety of pazopanib as adjuvant therapy in patients with localized or local advanced renal cell carcinoma after nephrectomy [in German]. Urologe A. 2011;50:489-492.http://www.ncbi.nlm.nih.gov/pubmed/21472622?tool=bestpractice.com
机器人辅助的减瘤性肾部分切除术
它是一个崭新的可替代腹腔镜的保留肾单位手术 (NSS)。该方法也达到了短期的肿瘤治疗目标，且手术发病率可能较低。[172]Benway BM, Bhaynani SB, Rogers CG, et al. Robot assisted partial nephrectomy versus laparoscopic partial nephrectomy for renal tumors: a multi-institutional analysis of perioperative outcomes. J Urol. 2009;182:866-872.http://www.ncbi.nlm.nih.gov/pubmed/19616229?tool=bestpractice.com
局部消融医疗程序
除了射频消融 (RFA) 和冷冻消融之外，还出现了其他局部消融技术，例如高强度聚焦超声 (HIFU)，其可用于适合接受治疗的肾脏肿块小的患者。[173]Caballero JM, Borrat P, Paraira M, et al. Extracorporeal high-intensity focused ultrasound: therapeutic alternative for renal tumors [in Spanish]. Actas Urol Esp. 2010;34:403-411.http://www.ncbi.nlm.nih.gov/pubmed/20470712?tool=bestpractice.com需要临床试验和长期数据采集以确定这些治疗长久的安全性和疗效。
树突状细胞疫苗
树突状细胞疫苗用于晚期 RCC 已在一些研究中显示了前景，但仍需更大规模的验证研究。若干小型研究的荟萃分析显示对RCC 有效率为 12%。[174]Draube A, Klein-González N, Mattheus S, et al. Dendritic cell based tumor vaccination in prostate and renal cell cancer: a systematic review and meta-analysis. PLoS ONE. 2011;6:e18801.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3080391/?tool=pubmedhttp://www.ncbi.nlm.nih.gov/pubmed/21533099?tool=bestpractice.com这一策略可能是未来治疗转移性疾病的一个选项，尤其是当发现了新的肿瘤抗原和免疫调节技术的时候。[175]Asemissen AM, Brossart P. Vaccination strategies in patients with renal cell carcinoma. Cancer Immunol Immunother. 2009;58:1169-1174.http://www.ncbi.nlm.nih.gov/pubmed/19360405?tool=bestpractice.com
患者自体疫苗
一些证据表明应用患者自体疫苗的辅助治疗（高危险 RCC 肾切除术后患者）可改善无进展生存期。[176]Jocham D, Richter A, Hoffmann L, et al. Adjuvant autologous renal tumour cell vaccine and risk of tumour progression in patients with renal-cell carcinoma after radical nephrectomy: phase III, randomised controlled trial. Lancet. 2004;363:594-599.http://www.ncbi.nlm.nih.gov/pubmed/14987883?tool=bestpractice.com因为当前针对应用酪氨酸激酶抑制剂作为辅助治疗手段的研究正在进行时，所以不清楚这一策略是否会被更广泛的调研。
