Everolimus延长了转移肾脏癌的无恶化存活
导读：
June 1, 2008 (芝加哥) —研究人员在美国临床肿瘤医学会第44届年会中发表指出，转移肾细胞癌(RCC)病患接受everolimus (RAD001)，相较于接受标准照护者，有明显较佳的无恶化存活；在6月时，使用everolimus治疗的病患中，有26%的RCC没有恶化；接受安慰剂者中，只有2%的RCC没有恶化；Everolimus组的平均无恶化存活4个月，安慰剂组为1.9个月
主要作者、纽约Sloan-Kettering纪念癌症中心总医师Robert J. Motzer表示，过去几年，肾细胞癌的治疗方式有很的改变，因为对其生物学知识和标靶治疗的发展有长足进步；使用sunitinib或者sorafenib治疗已经成为标准照护。
不过，使用sunitinib或者sorafenib治疗的病患还是有疾病恶化的可能，因此需要有效的治疗；Motzer医师表示，目还不符所需，有时候，病患对这些制剂发生阻抗性。
Everolimus是天然巨环内脂sirolimus的衍生物，具有免疫抑制和抗血管新生两种性质，其目标在于细胞蛋白质mTOR，与异常生长、增生、癌症细胞存活等讯息路径有关的调节子，除了RCC，它可以用来评估许癌症的治疗，包括淋巴瘤和神经内分泌瘤。
Everolimus在一个单组第二期转移RCC治疗前病患的试验中，显示出抗肿瘤活性；目前的是第三期研究，有410名转移RCC病患，在之前的治疗之后恶化；Motzer医师表示，本研究是全球性的，它是主要的治疗前组，许多病患接受过二或三种治疗。
病患随机接受everolimus(272 人)或者最佳的支持照护(138 人)，所有的病患之前都曾以其他制剂治疗：71%使用sunitinib、55%使用 sorafenib、26%使用sunitinib和sorafenib；初级终点是无恶化存活，由独立访谈确认。
Motzer医师表示，不是整体存活，因为考量到病患，我们希望有交叉时间点。
目前已经计划最后的分析，但是第二次的期中分析显示，服用everolimus的病患有相当大的好处；Everolimus组减少了70%的癌症恶化，风险比只有0.30；测定这点时，独立的监测委员会建议研究可以停止；研究在停止时并未整合，和everolimus比对，服用安慰剂的病患有81%出现疾病恶化。
此药物耐受不错，服用everolimus者有10%有需要停药的严重不良反应，安慰剂组有4%；因为不良反应需要减低剂量者，服用everolimus组有4%，安慰剂组不到1%。
Everolimus最常见的不良反应 研究组 口腔炎 贫血事件 无力 治疗 各种等级 36% 28% 28% 等级 3 或 4 4% 7% 2% 安慰剂 各种等级 7% 15% 20% 等级 3 或 4 0% 5% 4%
Motzer医师结论表示，转移肾细胞癌病患在使用sunitinib和 sorafenib之后恶化，服用Everolimus可以延长无恶化存活；这是在sunitinib和sorafenib无效之后，首次且唯一有确立临床效果的制剂，应透过当局的核准，作为标准照护。
未参与此研究的克里夫兰Taussig临床癌症中心、实质肿瘤科的Brian Rini医师表示，该研究结果是有效的，特别是因为目前没有建立RCC病患使用sunitinib和 sorafenib治疗之后恶化的标准照护，重点是，这不全然是第二线研究，对一些病患来说，可能是第三或第四线。
检视这些研究资料，Rini医师指出，肾脏癌的一个重要议题是更加了解阻抗的机转；他表示，这可以帮助决定后续治疗的选择，不论是针对不同的路径、或者是同一路径但不同方法、或者以更强效的方式针对路径；有一些正在进行的第三期研究或许可以为此带来一线希望。
美国临床肿瘤医学会(ASCO)第44届年会：摘要LBA5026。发表于2008年5月31日。摘要。
Everolimus Prolongs Progression-Free Survival in Metastatic Renal CancerBy Roxanne Nelson
June 1, 2008 (Chicago, Illinois) — Patients with metastatic renal cell carcinoma (RCC) who received everolimus (RAD001) had significantly better progression-free survival than those who received standard care, report researchers here at the American Society of Clinical Oncology 44th Annual Meeting. At 6 months, in patients treated with everolimus, RCC had not progressed in 26%; in those treated with placebo, RCC had not progressed in 2%. The median progression-free survival was 4 months in the everolimus group and 1.9 months in the placebo group."Over the past few years, there has been a dramatic change in the way we treat renal cell carcinoma, because of our growing knowledge of its biology and the development of targeted therapy," said lead author Robert J. Motzer, MD, attending physician at Memorial Sloan-Kettering Cancer Center, in New York, New York. "Treatment with sunitinib or sorafenib has become the standard of care."However, effective treatments are needed for patients who experience disease progression on sunitinib and sorafenib. "This is a setting of unmet need," said Dr. Motzer. "At some point all patients develop resistance to these agents."Everolimus is a derivative of the natural macrocyclic lactone sirolimus and has both immunosuppressant and antiangiogenic properties. It targets the cellular protein mTOR, a regulator of signaling pathways associated with the abnormal growth, proliferation, and survival of cancer cells. In addition to RCC, it is currently being evaluated in the treatment of several cancers, including lymphoma and neuroendocrinal tumors.Everolimus showed antitumor activity in a single-group phase?2 trial of pretreated patients with metastatic RCC. The current study was a phase?3 study of 410 patients with metastatic RCC who had progressed on previous treatment. "The study was conducted worldwide and it was a heavily pretreated group," Dr. Motzer. "Many patients had received 2 or 3 prior therapies."The patients were randomized to receive either everolimus (272 patients) or the best supportive care (138 patients). All of the patients had previously been treated with other agents: 71% with sunitinib, 55% with sorafenib, and 26% with sunitinib and sorafenib. The primary end point was progression-free survival, determined by independent review."It was not overall survival because of concerns for our patients," said Dr. Motzer. "We wanted the time for a crossover."A final analysis had been planned, but the second interim analysis showed that there was a large benefit for the patients taking everolimus. The everolimus group had a 70% decrease in cancer progression, with a strong hazard ratio of 0.30. When this was determined, the independent monitoring committee recommended that the study be discontinued. The study was unblended at the time it was stopped, and 81% of the patients taking placebo who had experienced disease progression crossed over to everolimus.The drug was relatively well tolerated. Adverse events in 10% of patients who received everolimus were severe enough to warrant discontinuation, compared with 4% in the placebo group. A reduction in dose, secondary to adverse events, was required by 4% of the everolimus group and less than 1% of the placebo group.[page]
Most Common Adverse Events With Everolimus Study Group Stomatitis Anemia Events Asthenia Treatment All grades 36% 28% 28% Grade?3 or 4 4% 7% 2% Placebo All grades 7% 15% 20% Grade?3 or 4 0% 5% 4%
"Everolimus prolongs progression-free survival in patients with metastatic renal cell carcinoma after they progress on sunitinib and sorafenib," Dr. Motzer concluded. "This is the first and only agent with established clinical benefit after sunitinib and sorafenib are no longer effective, and should be the standard of care in this setting pending approval by regulatory authorities."The results of the study are promising, especially because there is no established standard of care for RCC patients who have progressed after treatment with sunitinib and sorafenib, commented Brian Rini, MD, a staff member in the department of solid tumor oncology at the Cleveland Clinic Taussig Cancer Center, in Ohio, who was not involved in the study. "An important point is that this was not purely a second-line study, but more like a third or fourth line for some patients."When looking at the data in the context of sequential therapy, Dr. Rini pointed out that a critical issue in renal cancer is the better understanding of the mechanisms of resistance. This will help to "guide the choice of next treatment — whether we should target a different pathway, target the same pathway but in a different way, or target the pathway in a more potent manner," he said. "There are some ongoing phase?3 studies that might be able to shed some light on this."American Society of Clinical Oncology (ASCO) 44th Annual Meeting: Abstract LBA5026. Presented May 31, 2008. Abstract声明：该作品系作者结合法律法规，政府官网及互联网相关知识整合，如若内容错误请通过【投诉】功能联系删除.
相关知识推荐
误诊，即医务人员由于观察检查不周，不认真不仔细，导致漏诊或给出错误的诊断。误诊的后果往往可能是较大的，因此我国对误诊也做出了比较严格的规定。那么，医院误诊有哪些
我们知道，子女抚养权问题通常都是男女双方发生争议的焦点，双方都想获得子女的抚养权，在双方达不成一致意见的情况下，只能由法官自由裁量，考虑多方面因素来判决抚养权归
医疗事故赔偿纠纷的诉讼时效为三年，应当自受害人自权利人知道或者应当知道权利受到损害以及义务人之日起计算。我国《医疗事故处理条例》规定，发生医疗事故争议，当事人申
医疗事故中医院若不予赔偿的，当事人可以与医院协商解决，协商不成的，可以向人民法院提起诉讼。我国《医疗事故处理条例》规定，发生医疗事故的赔偿等民事责任争议，医患双
医疗纠纷中的当事人对人民法院作出的调解协议书反悔了的，无法自行撤销，必须经人民法院认定调解协议无效之后才可以重新达成新调解协议或者提起诉讼。我国《人民调解法》规
医疗机构不承担赔偿责任的情形包括有：患者或者其近亲属不配合医疗机构进行符合诊疗规范的诊疗的；医务人员在抢救生命垂危的患者等紧急情况下已经尽到合理诊疗义务的；限于
医院出伪证若是构成伪证罪的，会被处三年以下有期徒刑或者拘役。情节严重的，处三年以上七年以下有期徒刑。伪证罪是指在刑事诉讼中，证人、鉴定人、记录人、翻译人对与案件
