本帖最後由 lsc0019 於 2009-4-2 00:54 編輯
作者：Nick Mulcahy
出處：WebMD醫學新聞
March 16, 2009(佛州好萊塢) — 紐約市Sloan-Kettering癌症紀念中心的Robert J. Motzer醫師在國際綜合癌症網絡(NCCN)第14屆年會中表示，腎臟癌的新治療方法讓末期病患產生更久的整體存活，且創造此疾病治療上令人振奮的時光。
他在發表NCCN腎臟癌治療指引更新版時表示，有許多治療選項，且越來越多。
不過，此一領域仍有許多挑戰，包括新標靶治療的高花費，多數末期病患的緩和需求持續增加。
然而，Motzer醫師的最大顧慮是，新治療選項之外的議題。他向Medscape Oncology表示，我們必須確保提供病患這些藥物。仍有轉移腎臟癌病患僅由泌尿科醫師治療，而非一個醫療團隊，這些病患就比較不會接受到最新的治療選項。
他指出，轉移腎臟細胞癌病患的展望是黯淡無望的，整體約有30%病患發生轉移性疾病，而這些人的五年存活率不到10%。
他解釋，但是這些已經改變。
例如，於2008年美國臨床腫瘤學會發表的一篇研究中，標靶治療藥物sunitinib(Sutent，輝瑞藥廠)獲得轉移疾病患者平均整體存活26.4個月，當時由Medscape Oncology加以報導；他表示，之前用老一代藥物進行的研究，平均整體存活是12個月。
他形容sunitinib試驗為，轉移性疾病治療已經有新的存活率成果。
現在，新的標靶治療專門用於疾病轉移的患者；不過，歐美的臨床試驗正探究將這些新藥用於輔助治療之後進行手術的情況，也就是將標靶治療作為手術輔助治療的考量。
【指引改變：先標靶治療】
Motzer醫師表示，基本上，第一、二和三期局部腎臟癌以手術切除，不論是部份或根除；第四期病患主要是轉移疾病者，通常也接受手術，但是可以在初步治療後接受藥物治療。
對於局部疾病復發的病患以及第四期病患，NCCN分類一的高度建議第一線治療是sunitinib、temsirolimus (Torisel，Wyeth藥廠；分類一僅用於預後不佳的病患)以及bevacizumab(Avastin，Genentech藥廠)加上干擾素；後者獲得歐洲核准，美國則尚未核准。
Motzer醫師指出，這些指引用於細胞組織學清楚的病患，對於少數細胞組織學不清楚的病患，優先的第一線治療是臨床試驗。
對於第一線治療後惡化的病患，下一步驟是後續治療。Motzer醫師解釋，一般來說，我們提供一種治療，之後再惡化時換成另外一種。他表示，第二線治療包括sorafenib(Nevaxar，Bayer藥廠)。不過，如果病患第一次是使用較舊的細胞激素(如干擾素)治療的話，後續或第二線治療可以包括sunitinib。
Motzer醫師指出，NCCN的腎臟癌指引在過去幾年間，有關轉移性疾病有很大的改變。
NCCN的Joan McClure表示，實際上，新治療已經改變腎臟癌的照護模式；她在聲明中表示，腎臟癌實際上已經變成需要持續照護的類型，就像大腸癌；現有的第二線治療用於曾經以特定製劑治療的病患。
【預測存活】
NCCN 腎臟癌指引使用Sloan-Kettering癌症紀念中心發展的評分系統，以預測所有腎細胞癌病患的存活。
Motzer醫師表示，有下列項目三種以上的病患視為預後不佳，這類病患的平均存活為5個月，這些項目包括：
* 乳酸脫氫酶值超過正常上限1.5倍；
* 血色素值低於正常值；
* 校正血清鈣值超過10 mg/dL；
* 從最初診斷變成開始全身性治療的期間不到1年；
* Karnofsky氏體能表現分數低於70；且
* 兩處以上器官轉移。
Motzer醫師表示，都沒有這些風險因素的病患，其平均存活為30個月，一或兩種種風險因素的病患，其平均存活為14個月。
【新臨床試驗、新製劑】
第一線sunitinib治療失敗之末期病患，使用temsirolimus 或 sorafenib進行第二線治療的臨床比較試驗中，在美國，temsirolimus的第三期試驗結果目前限用於預後不佳之病患，即使該藥物對末期腎臟癌有比較廣泛的適應症。Motzer醫師表示，在轉移病患使用sunitinib之後仍惡化的病患，有極高的興趣使用此藥物。
在轉移病患進行臨床試驗的其他製劑有everolimus (Novartis藥廠)、pazopanib (GlaxoSmithKline藥廠)、以及axitinib (輝瑞藥廠)。這三種產品都還在研發階段且尚未獲得核准。
Motzer醫師是GlaxoSmithKline與Novartis的顧問，且擔任Bayer HeatlhCare的發言人。他也接受Genentech、GlaxoSmithKline以及Novartis等的資金與研究支持。
國際綜合癌症網絡(NCCN)第14屆年會。發表於2009年3月13日。
NCCN 2009: Survival Increases as Drug Options Grow in Kidney Cancer
By Nick Mulcahy
Medscape Medical News
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 on the speakers’ 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. |
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