Reeves David J, Liu Chin Y
Department of Pharmacy Services, Karmanos Cancer Center, Detroit, MI 48201, USA.
Cancer Chemother Pharmacol. 2009 Jun;64(1):11-25. doi: 10.1007/s00280-009-0983-z. Epub 2009 Apr 3.
To review the treatment of metastatic renal cell carcinoma (RCC), including the use of new targeted therapies.
A search of MEDLINE (1966 to August 2008) and American Society of Clinical Oncology Meeting abstracts (2005 to May 2008) was preformed using the search terms bevacizumab, everolimus, interferon-alfa (IFN-alpha), interleukin-2 (IL-2), sorafenib, sunitinib, temsirolimus, and RCC. Articles most pertinent to the treatment of metastatic RCC are reviewed.
The treatment of metastatic RCC has undergone a paradigm shift over the past 5 years from biologic response modifiers to new targeted therapies. Historically, response rates for the biological response modifiers, aldesleukin (IL-2), and IFN-alpha were approximately 15%. Recently, three targeted agents, sorafenib, sunitinib, and temsirolimus have been approved for the treatment of RCC. Additionally, bevacizumab has been investigated and shown to increase progression free survival in RCC. IL-2 remains the only agent to induce complete, durable remissions; however, many patients are not eligible for this therapy. Newer agents (sorafenib, sunitinib, and temsirolimus) have shown to be superior to IFN-alpha or placebo and bevacizumab combined with IFN-alpha has shown activity when compared to IFN-alpha alone. Unlike IL-2, the greatest benefit obtained with targeted therapies is in achieving stable disease (SD). Despite their benefit, targeted therapies have never been compared with each other in clinical trials and choosing the most appropriate agent remains challenging. To date, the optimal sequence or combination of treatments has not been defined; however, everolimus has recently demonstrated activity in patients progressing on targeted therapy.
IL-2 remains the most active regimen in inducing complete responses; however, its use is accompanied by substantial morbidity and is limited to those with a good performance status. Targeted therapies are also efficacious in the treatment of RCC, with the major benefit being induction of SD. Future research will better define the sequencing of therapies, as well as, explore the activity of novel combination regimens.
回顾转移性肾细胞癌（RCC）的治疗方法，包括新型靶向治疗的应用。
使用贝伐单抗、依维莫司、干扰素-α（IFN-α）、白细胞介素-2（IL-2）、索拉非尼、舒尼替尼、替西罗莫司和RCC等检索词，对MEDLINE（1966年至2008年8月）和美国临床肿瘤学会会议摘要（2005年至2008年5月）进行检索。对与转移性RCC治疗最相关的文章进行综述。
在过去5年中，转移性RCC的治疗已从生物反应调节剂转向新型靶向治疗，发生了模式转变。从历史上看，生物反应调节剂、阿地白介素（IL-2）和IFN-α的缓解率约为15%。最近，三种靶向药物索拉非尼、舒尼替尼和替西罗莫司已被批准用于治疗RCC。此外，贝伐单抗已被研究并显示可提高RCC的无进展生存期。IL-2仍然是唯一能诱导完全、持久缓解的药物；然而，许多患者不符合该治疗条件。新型药物（索拉非尼、舒尼替尼和替西罗莫司）已显示优于IFN-α或安慰剂，并且与单独使用IFN-α相比，贝伐单抗联合IFN-α已显示出活性。与IL-2不同，靶向治疗获得的最大益处是实现疾病稳定（SD）。尽管它们有好处，但靶向治疗在临床试验中从未相互比较过，选择最合适的药物仍然具有挑战性。迄今为止，尚未确定最佳的治疗顺序或联合方案；然而，依维莫司最近已在接受靶向治疗进展的患者中显示出活性。
IL-2仍然是诱导完全缓解最有效的方案；然而，其使用伴随着相当大的发病率，并且仅限于那些身体状况良好的患者。靶向治疗在RCC治疗中也有效，主要益处是诱导SD。未来的研究将更好地确定治疗顺序，并探索新型联合方案的活性。
