纽约市Sloan-Kettering癌症纪念中心的Robert J. Motzer医师在国际综合癌症网络(NCCN)第14届年会中表示，肾脏癌的新治疗方法让末期病患產生更久的整体存活，且创造此疾病治疗上令人振奋的时光。
他在发表NCCN肾脏癌治疗指引更新版时表示，有许多治疗选项，且越来越多。
不过，此一领域仍有许多挑战，包括新标靶治疗的高花费，多数末期病患的缓和需求持续增加。
然而，Motzer医师的最大顾虑是，新治疗选项之外的议题。他向Medscape Oncology表示，我们必须确保提供病患这些药物。仍有转移肾脏癌病患仅由泌尿科医师治疗，而非一个医疗团队，这些病患就比较不会接受到最新的治疗选项。
他指出，转移肾脏细胞癌病患的展望是黯淡无望的，整体约有30%病患发生转移性疾病，而这些人的五年存活率不到10%。
他解释，但是这些已经改变。
例如，于2008年美国临床肿瘤学会发表的一篇研究中，标靶治疗药物sunitinib(Sutent，辉瑞药厂)获得转移疾病患者平均整体存活26.4个月，当时由Medscape Oncology加以报导；他表示，之前用老一代药物进行的研究，平均整体存活是12个月。
他形容sunitinib试验为，转移性疾病治疗已经有新的存活率成果。
现在，新的标靶治疗专门用于疾病转移的患者；不过，欧美的临床试验正探究将这些新药用于辅助治疗之后进行手术的情况，也就是将标靶治疗作为手术辅助治疗的考量。
【指引改变：先标靶治疗】
Motzer医师表示，基本上，第一、二和三期局部肾脏癌以手术切除，不论是部份或根除；第四期病患主要是转移疾病者，通常也接受手术，但是可以在初步治疗后接受药物治疗。
对于局部疾病復发的病患以及第四期病患，NCCN分类一的高度建议第一线治疗是sunitinib、temsirolimus (Torisel，Wyeth药厂；分类一仅用于预后不佳的病患)以及bevacizumab(Avastin，Genentech药厂)加上干扰素；后者获得欧洲核准，美国则尚未核准。
Motzer医师指出，这些指引用于细胞组织学清楚的病患，对于少数细胞组织学不清楚的病患，优先的第一线治疗是临床试验。
对于第一线治疗后恶化的病患，下一步骤是后续治疗。Motzer医师解释，一般来说，我们提供一种治疗，之后再恶化时换成另外一种。他表示，第二线治疗包括sorafenib(Nevaxar，Bayer药厂)。不过，如果病患第一次是使用较旧的细胞激素(如干扰素)治疗的话，后续或第二线治疗可以包括sunitinib。
Motzer医师指出，NCCN的肾脏癌指引在过去几年间，有关转移性疾病有很大的改变。
NCCN的Joan McClure表示，实际上，新治疗已经改变肾脏癌的照护模式；她在声明中表示，肾脏癌实际上已经变成需要持续照护的类型，就像大肠癌；现有的第二线治疗用于曾经以特定製剂治疗的病患。
【预测存活】
NCCN 肾脏癌指引使用Sloan-Kettering癌症纪念中心发展的评分系统，以预测所有肾细胞癌病患的存活。
Motzer医师表示，有下列项目三种以上的病患视为预后不佳，这类病患的平均存活为5个月，这些项目包括：
* 乳酸脱氢酶值超过正常上限1.5倍；
* 血色素值低于正常值；
* 校正血清钙值超过10 mg/dL；
* 从最初诊断变成开始全身性治疗的期间不到1年；
* Karnofsky氏体能表现分数低于70；且
* 两处以上器官转移。
Motzer医师表示，都没有这些风险因素的病患，其平均存活为30个月，一或两种种风险因素的病患，其平均存活为14个月。
【新临床试验、新製剂】
第一线sunitinib治疗失败之末期病患，使用temsirolimus 或 sorafenib进行第二线治疗的临床比较试验中，在美国，temsirolimus的第三期试验结果目前限用于预后不佳之病患，即使该药物对末期肾脏癌有比较广泛的适应症。Motzer医师表示，在转移病患使用sunitinib之后仍恶化的病患，有极高的兴趣使用此药物。
在转移病患进行临床试验的其他製剂有everolimus (Novartis药厂)、pazopanib (GlaxoSmithKline药厂)、以及axitinib (辉瑞药厂)。这三种產品都还在研发阶段且尚未获得核准。
Motzer医师是GlaxoSmithKline与Novartis的顾问，且担任Bayer HeatlhCare的发言人。他也接受Genentech、GlaxoSmithKline以及Novartis等的资金与研究支持。
国际综合癌症网络(NCCN)第14届年会。发表于2009年3月13日。
NCCN 2009: Survival Increases as Drug Options Grow in Kidney Cancer
March 16, 2009 (Hollywood, Florida) — New treatments for kidney cancer have produced \"much longer\" overall survival with advanced disease and created a \"very exciting time\" in the treatment of the disease, said Robert J. Motzer, MD, from Memorial Sloan-Kettering Cancer Center, in New York City, here at the National Comprehensive Cancer Network (NCCN) 14th Annual Conference.
\"There are lots of treatment options, and more are coming,\" he said during a session updating the NCCN\'s kidney cancer guidelines.
However, there are still many challenges in the field, including the high cost of the new targeted therapies and the fact that most advanced patients have an ongoing palliative need for the drugs, he added
We have to make sure that patients are offered these drugs.
Nevertheless, Dr. Motzer\'s great concern is that the word get out about new treatment options. \"We have to make sure that patients are offered these drugs,\" he told Medscape Oncology. \"There are still metastatic kidney cancer patients being treated soley by urologists, rather than by a team approach, for example,\" he said, suggesting that such patients would not likely receive the latest treatment options.
\"The outlook for patients with metastatic renal cell cancer has been bleak,\" he added. About 30% of all patients will develop metastatic disease and the 5-year survival rate for those patients is less than 10%, he observed.
\"But things have changed here,\" he explained.
A new bar for survival has been set in the treatment of metastatic disease.
For instance, in a study presented at the American Society of Clinical Oncology meeting in 2008, the targeted therapy sunitinib (Sutent, Pfizer) produced a median overall survival of 26.4 months in patients with metastatic disease, as reported by Medscape Oncology. \"Previously [in studies of the older generation of drugs], average overall survival was 12 months,\" he said.
\"A new bar for survival has been set in the treatment of metastatic disease,\" he said about the sunitinib trial.
There is considerable interest in using targeted therapies as an adjuvant to surgery.
The new targeted therapies are, for now, used exclusively in patients with metastatic disease. However, clinical trials in Europe and the United States are underway to test the new drugs in the adjuvant setting, following surgery. \"There is considerable interest in using targeted therapies as an adjuvant to surgery,\" he added.
Guideline Changes: Targeted Therapies to the Fore
The \"cornerstone\" for stage?1, 2, and 3 local kidney cancers is surgical excision, either partial or radical, said Dr. Motzer. Patients with stage?4 disease, who are mainly those with metastatic disease, usually undergo surgery as well, but receive drug therapy after this primary treatment.
For those patients with local disease who relapse and for those with stage?4 disease, the first-line therapies with a category?1 designation from NCCN (highest recommendation) are sunitinib, temsirolimus (Torisel, Wyeth; category?1 for poor-prognosis patients only), and bevacizumab (Avastin, Genentech) plus interferon. The latter is approved in Europe but not the United States.
Dr. Motzer noted that these guidelines are for patients with clear cell histology. For those with nonclear cell histology, who are a small minority, the preferred first-line therapy is a clinical trial.
For patients who progress on first-line therapy, the next step is subsequent therapy. \"Generally, we offer one therapy and then switch to another at the time of progression,\" explained Dr. Motzer. Second-line therapies include sorafenib (Nevaxar, Bayer), he said. However, subsequent or second-line therapy can include sunitinib if the patient was first receiving an older cytokine therapy, such as interferon.
Dr. Motzer noted that the NCCN guidelines for kidney cancer have \"changed the most in metastatic disease in the past few years.\"
In effect, the new therapies have changed the model of care for kidney cancer, said Joan McClure, MS, from the NCCN. \"Kidney cancer is actually moving into a continuum-of-care paradigm, much like that for colon cancer,\" she said in a statement. \"Second-line therapies now exist for patients who have previously been treated with specific agents.\"
Predictors of Survival The NCCN kidney cancer guidelines use a scoring system developed at Memorial Sloan-Kettering to help predict survival in all renal cell cancer patients.
The prognosis for patients with 3 or more of the following items is defined as poor, and such patients have a median survival of 5 months, said Dr. Motzer. The predictive items are:
lactate dehydrogenase level of more than 1.5 times the upper limit of normal; hemoglobin level lower than normal; corrected serum calcium level of more than 10?mg/dL; interval of less than 1 year from original diagnosis to the start of systemic therapy; Karnofsky performance score of 70 or less; and 2 or more sites of organ metastasis.
Patients with none of these risk factors have a median survival of 30 months. Patients with 1 or 2 risk factors have a median survival of 14 months, said Dr. Motzer.
New Clinical Trials, New Agents
Among the new trials in advanced patients is a comparison of temsirolimus with sorafenib as a second-line therapy in patients who have failed first-line sunitinib. In the United States, phase 3 trial results for temsirolimus are currently limited to patients with a poor prognosis, even though the drug has a broad indication for the treatment of advanced kidney cancer. \"There is a high level of interest in using this following sunitinib progression in patients with metastatic disease,\" said Dr. Motzer.
Other agents being tested in clinical trials in patients with metastatic disease are everolimus (Novartis), pazopanib (GlaxoSmithKline), and axitinib (Pfizer). All 3 products are still under development and not yet available.
Dr. Motzer is a consultant to GlaxoSmithKline and Novartis and is onthespeakers’ bureau of Bayer HeatlhCare. He has also received grant/research
support from Genentech, GlaxoSmithKline, and Novartis.
National Comprehensive Cancer Network (NCCN) 14th Annual Conference. Presented March 13, 2009.