Sorafenib在第2期研究中顯示對乳癌有效


  September 23, 2009 (德國柏林) — 在一篇第2b期研究中,Sorafenib(商品名Nexavar)顯示對乳癌有效,現在計畫進行後續研究。
  
  前述結果發表於第15屆歐洲癌症組織研討會與第34屆歐洲腫瘤醫學會年會聯合研討會中的理事長講座。
  
  相較於單用capecitabine,Sorafenib加上capecitabine(商品名Xeloda)可顯著改善局部末期或轉移乳癌的無惡化存活。
  
  主要研究者、西班牙巴塞隆納Vall d'Hebron腫瘤研究中心內科教授Jose Baselga醫師表示,事實是這兩種口服藥物對於乳癌病患來說,是獨特且方便的治療選項。
  
  目前,Sorafenib適應症為用於腎細胞腫瘤以及肝細胞腫瘤。Baselga醫師解釋,嘗試用它來治療乳癌是因為最近有一些研究顯示,有清楚的證據指出血管新生相當重要。
  
  在bevacizumab(商品名Avastin)的研究中,抑制血管新生對於乳癌有幫助,bevacizumab獲得美國食品藥物管理局加速核准用於此適應症。
  
  奧斯陸Norwegian Radium醫院的Anne-Lisa Borresen-Dale博士指出,Sorafenib是這個方式的另一個步驟,不過它作用在更多標靶且是口服藥。Bevacizumab作用在對抗血管內皮細胞生長因子(VEGF)接受器;sorafenib除了抑制VEGF,也作用在血小板衍生生長因子受體以及許多其他的酪胺酸激酶。
  
  Borresen-Dale博士向Medscape Oncology表示,這表示sorafenib提供一種較廣泛的方法。這並不一定意味著它有較大的臨床影響,但是個值得一試的想法,迄今為止,結果相當有效。
  
  【增加無惡化存活】
  Baselga醫師解釋,稱為SOLTI-0701的此一試驗,比較了sorafenib加capecitabine以及單用capecitabine。每天給予兩次的Sorafenib 400 mg,每21天給予14天、每天2次的capecitabine1000 mg/m2,這是一般用於臨床實務的劑量,且略低於核准的劑量(1250 mg/m2)。
  
  研究對象是229名無法切除的局部惡化或轉移乳癌(HER-陰性)病患,之前只接受過1次或未曾接受過化療療程。
  
  併用組的無惡化存活中位數(6.4個月)顯著較高,單用capecitabine組為4.1個月(P= .0006),風險比(HR)為0.576 (95%信心區間:0.410- 0.809)。
  
  Baselga醫師表示,這顯示疾病惡化風險降低42%。
  
  他報告指出,在之前未曾接受過化療(第一線HR,0.498)的病患中,以及曾經接受過1次處方(第二線HR,0.652)的病患中,無惡化存活的差異有統計上的顯著意義。
  
  他向與會聽眾表示,不過,整體反應沒有顯著差異,我們仍在等待整體存活的資料。
  
  併用sorafenib與capecitabine治療的病患有較多人發生手足症候群,併用組有15人(13.4%)因為副作用退出試驗,單用capecitabine組則只有9人(8%)退出。
  
  但是Baselga醫師指出,併用是可耐受的,副作用多數可以控制。並沒有新的或意料外的副作用。
  
  Baselga醫師表示,結果認為sorafenib值得加入乳癌病患的化療中。
  
  Onyx公司以及sorafenib 的製造商、Bayer公司資助本研究。
  
  第15屆歐洲癌症組織研討會(ECCO 15)與第34屆歐洲腫瘤醫學會年會(34th ESMO)聯合研討會:摘要3LBA。發表於2009年9月23日。
  

Sorafenib Shows Promise in Breast Cancer in Phase 2 Study

By Zosia Chustecka
Medscape Medical News

September 23, 2009 (Berlin, Germany) — Sorafenib (Nexavar) has shown promise in breast cancer in a phase?2b trial, and further studies are now planned.

The results were presented here at a presidential session of the 15th Congress of the European CanCer Organization and the 34th European Society for Medical Oncology Multidisciplinary Congress.

Sorafenib added to capecitabine (Xeloda) significantly improved progression-free survival, compared with capecitabine alone, in locally advanced or metastatic breast cancer.

The fact that both drugs were administered orally "may represent a unique and convenient treatment option for patients with breast cancer," said principal investigator Jose Baselga, MD, professor of medicine at the Vall d'Hebron Institute of Oncology in Barcelona, Spain.

Sorafenib is currently indicated for use in renal cell carcinoma and hepatocellular carcinoma. It was tried in breast cancer because a number of recent studies have shown "clear evidence that the role of angiogenesis is critically important," Dr. Baselga explained.

Inhibition of angiogenesis has been shown to be beneficial in breast cancer in studies with bevacizumab (Avastin), which received accelerated approval from the US Food and Drug Administration for this indication.

Sorafenib is another step in this approach, but it is active on many more targets and is also an oral drug, noted Anne-Lisa Borresen-Dale, PhD, from the Norwegian Radium Hospital in Oslo. Bevacizumab is active against the vascular endothelial growth-factor (VEGF) receptor; sorafenib, in addition to inhibiting VEGF, acts on the platelet-derived growth-factor receptor and several other tyrosine kinases.

"This means that sorafenib offers a broader approach," Dr. Borresen-Dale told Medscape Oncology. This does not necessarily mean that it will have a bigger clinical impact, but "it is an interesting idea to test," she said, adding that the results so far have been "very promising."

Increase in Progression-Free Survival

The new study, known as SOLTI-0701, compared sorafenib plus capecitabine with capecitabine alone. Sorafenib 400?mg was given twice daily, and capecitabine1000?mg/m2 was given twice daily for 14 of every 21 days, which is the dose that is normally used in clinical practice and slightly lower than the dose that was approved (1250?mg/m2), Dr. Baselga explained.

The study was conducted in 229 patients with unresectable locally advanced or metastatic breast cancer (HER-negative), who had previously undergone only 1 course of or no chemotherapy.

Median progression-free survival was significantly higher in the combination group (6.4 vs 4.1 months for capecitabine alone; P?= .0006), with a hazard ratio (HR) of 0.576 (95% confidence interval 0.410?- 0.809).

"This shows a 42% reduction in the risk of disease progression," Dr. Baselga said.

The difference in progression-free survival was statistically significant in patients who had not received any previous chemotherapy (first line HR, 0.498) and in those who had already received 1 previous regimen (second line HR, 0.652), he reported.

However, there was no significant difference in the overall response, and "we are still waiting for data on overall survival," he told meeting attendees.

There was a higher incidence of hand and foot syndrome in patients who were treated with the combination of sorafenib and capecitabine, and 15 patients (13.4%) taking the combination withdrew from the trial because of adverse effects, whereas only 9 patients (8%) taking capecitabine alone did.

But Dr. Baselga noted that the combination "was tolerable and the side effects were mostly manageable. No new or unexpected side effects were observed."

"The results suggest that sorafenib may be a valuable addition to chemotherapy in breast cancer," Dr. Baselga said.

The study was funded by Onyx and Bayer, the manufacturers of sorafenib.

15th Congress of the European CanCer Organization (ECCO 15) and the 34th European Society for Medical Oncology (34th ESMO) Multidisciplinary Congress: Abstract 3LBA. Presented September 23, 2009.

    
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