作者：Zosia Chustecka 出處：WebMD醫學新聞 【24drs.com】March 23, 2010
一項新的綜合分析支持已切除非小細胞肺癌（NSCLC）病患使用輔助化學治療。
來自安納堡密西根大學內科部的Gregory Kalemkerian醫師表示，雖然存活好處看起來是很小的，但世界各地採用輔助化療每年可以拯救10,000條性命。他撰寫這項研究之後的主編評論，兩篇文章都線上發表在3月24日的Lancet期刊。
Kalemkerian醫師寫到，但是輔助化學治療已經應用於該病患族群，因此，這些新研究結果，建立在同一研究團隊過去兩項綜合分析，對臨床執業的附加價值不高。
西雅圖瑞典癌症機構的胸腔腫瘤科醫療主任、Medscape腫瘤學部落格H. Jack West醫師同意，他表示，綜合分析結果告訴我們的，幾乎超過每位胸腔腫瘤醫師已經確認的事實嗎？
West醫師表示，許多嚴謹的前瞻性第三期隨機分派研究已經確立，符合許多可以考慮術後化學治療之足夠風險疾病適當患者接受輔助化學治療的好處，這些病患部分接受了目前較新的化學治療療程。對我來說，加上許多很久以前進行的、使用不同分期方法以及受到質疑之治療療程的較不嚴謹研究結果，對這個問題的價值有多少仍然是未知的。
West醫師指出，這個問題在這項綜合分析之前已經被回答了，且對我來說，唯一釐清的是，好處仍然是有的，儘管以許多品質較差的研究稀釋高品質研究結果之後。如果某些人過去質疑輔助性化療的可用性，現在因為這項綜合分析而變得比較有信心，我將覺得驚訝。
West醫師向Medscape腫瘤學表示，我們不應該將「更多的數據」與「更好的數據」混為一談。
【新的文獻包括這兩項綜合分析】
這篇新的文獻確實包括這兩項綜合分析，且各自達到同樣的結論，可手術的NSCLC患者，術後加上輔助化學治療可以改善預後，不論是否包括放射線治療。
這項新的綜合分析第一個針對的是34項臨床研究中，8447位（3323位死亡）病患術後加上化學治療的效果。發現5年存活率增加了4%，從60%增加到64%（危險比值[HR]為0.86；P<0.0001）。第二項綜合分析針對13項臨床研究中，2660位病患（1909未死亡）術後化學治療加上放射線治療的好處。也發現5年存活率增加了4%，從29%增加到33%（HR為0.88；P=0.009）。
這些研究結果由英國倫敦醫學研究局臨床試驗單位的Sarah Burdett碩士，以及法國Villejuif Gustave Roussy機構的Jean-Pierre Pignon醫師報告，代表NSCLC綜合分析聯合團隊。
Kalemkerian醫師指出，該團隊過去也發表過兩項類似綜合分析。
1995年，他們報告5年存活率增加5%，以cisplatin為主的化學治療，未達到統計上顯著差異（HR為0.87；P=0.08）（BMJ. 1995; 311: 899-909）。
最近，同樣一個團隊發表了LACE綜合分析（J Clin Oncol. 2008; 26: 5043-5051），僅收納現今cisplatin為主的療程，結果發現5年存活率顯著改善5.4%（HR為0.89；P=0.005）。
主編們的結論是，最新的研究結果添加了已切除腫瘤之NSCLC患者使用輔助化學治療的證據。
【建議的化學治療】
在他的主編評論中，Kalemkerian醫師也總結了目前的臨床執業方法。
他寫到，第2到第3期NSCLC患者，完全切除腫瘤後，且在術後3個月恢復完全，身體狀況良好，建議接受以鉑金類藥物為基礎的化學治療。
如果病患腫瘤很大（T2b、T3），且沒有侵犯到淋巴結，也可以考慮治療。
Kalemkerian醫師提醒，然而，數據的缺乏代表第1a期患者並不建議接受輔助化學治療。而年齡超過70歲病患的研究數據同樣不多，這個族群患者接受輔助化學治療應特別謹慎。
他建議，未來的研究應該針對這些次級族群使用輔助化學治療的角色進行探討，以及使用生化標記選擇誰將會因為特定治療而受益。
研究者們表示已無相關資金上的往來。
More Support for Adjuvant Chemo in Resected NSCLC
By Zosia Chustecka
Medscape Medical News
March 23, 2010 — A new meta-analysis adds support for the use of adjuvant chemotherapy in patients with resected nonsmall-cell lung cancer (NSCLC).
"Although the survival benefit seems small, worldwide adoption of adjuvant chemotherapy could save up to 10,000 lives every year," said Gregory Kalemkerian, MD, from the Department of Internal Medicine at the University of Michigan in Ann Arbor. He was writing in an editorial that accompanies the results, both of which were published online March 24 in The Lancet.
But adjuvant chemotherapy is already used in this patient population. Hence, the new results, which build on 2 previous meta-analyses from the same group, "add little to clinical practice," the Dr. Kalemkerian writes.
Medscape Oncology blogger H. Jack West, MD, medical director of thoracic oncology at the Swedish Cancer Institute in Seattle , Washington , agrees: "What has the meta-analysis told us, beyond confirming what was already established by nearly every thoracic oncologist?"
"The benefit of adjuvant chemotherapy in appropriate patients with sufficiently high-risk disease who are fit enough to consider postoperative chemotherapy has already been well established by several well conducted prospective randomized phase 3 trials, some using relatively current chemotherapy regimens," Dr. West said. "It is unclear to me what value there is in adding a wide range of very old and less well conducted studies that use varied staging and questionable treatment regimens to address the issue."
We should not confuse 'more data' with 'better data.'
"This question had already been answered before this meta-analysis, and to me the only issue that this clarifies is that the benefit is still present, despite diluting the results of high-quality studies with multiple inferior ones," Dr. West said. "I would be very surprised if someone who previously doubted the utility of adjuvant chemotherapy became convinced on the basis of this meta-analysis."
"We should not confuse 'more data' with 'better data'," Dr. West told Medscape Oncology.
New Paper Comprises 2 Meta-Analyses
The new paper actually comprises 2 meta-analyses, and both reach the same conclusion — that the addition of adjuvant chemotherapy after surgery for patients with operable NSCLC improves survival, irrespective of whether radiotherapy was included.
The first of these new meta-analyses looked at adding chemotherapy alone after surgery in 8447 patients (3323 deaths) from 34 clinical trials. It found an absolute increase in survival of 4% at 5 years, from 60% to 64% (hazard ratio [HR], 0.86; P< .0001). The second meta-analysis looked at chemotherapy plus radiotherapy after surgery in 2660 patients (1909 deaths) from 13 trials. It also found an absolute increase in survival of 4% at 5 years, from 29% to 33% (HR, 0.88; P=.009).
These results are reported by Sarah Burdett, MSc, from the Medical Research Council Clinical Trials Unit in London, United Kingdom, and Jean-Pierre Pignon, MD, from the Institut Gustave Roussy in Villejuif, France, on behalf of the NSCLC Meta-Analyses Collaborative Group.
This group has reported 2 previous meta-analyses, Dr. Kalemkerian points out.
In 1995, they reported a 5% improvement in 5-year survival, which was not statistically significant (HR, 0.87; P= .08) with cisplatin-based chemotherapy (BMJ. 1995;311:899-909).
More recently, the same group reported the LACE meta-analysis (J Clin Oncol. 2008;26:5043-5051), which included only trials that used modern cisplatin-based regimens, and found a significant 5-year survival benefit of 5.4% (HR, 0.89; P?= .005).
The latest results "add further support to the use of adjuvant chemotherapy in patients with resected NSCLC," the editorialist concludes.
Chemotherapy Recommended
In his editorial, Dr. Kalemkerian also summarizes the current clinical practice.
"Adjuvant platinum-based chemotherapy can be recommended for patients who have complete resection of stage2 to 3 NSCLC and have uncomplicated recovery with good performance status within 3 months of surgery," he writes.
"Treatment can be considered for patients with larger tumors (T2b, T3) without lymph node involvement," he adds.
However, the scarcity of data means that adjuvant treatment cannot be recommended for patients with stage 1a disease, Dr. Kalemkerian warns. "Similarly, data for patients older than 70 years are sparse, and adjuvant chemotherapy should be approached with caution in the population."
Future studies should focus on the role of adjuvant therapy in these subgroups, and on the use of biomarkers to select patients who will benefit from specific treatments, he suggests.
The researchers have disclosed no relevant financial relationships.
Lancet. Published online March?24, 2010.
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