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作者：Caroline Helwick  
出處：WebMD醫學新聞

　　January 22（佛州奧蘭多）－過去研究顯示老年大腸直腸癌患者接受較新化學治療並無好處，一項隨機分派第三期臨床研究結果發現，以輔助capecitabine與oxaliplatin（XELOX）相較於標準5-fluorouracil與leucovorin（5-FU/LV）治療預後更好。這些研究結果來自NO16968研究的次組分析，這項研究比較輔助XELOX與標準化學治療對於第三期癌症病患的效果。
　　
　　費城賓州大學Abramson癌症中心Deenie Greitzer腸胃腫瘤科教授Daniel G. Haller醫師表示，超過一半新診斷罹患大腸直腸癌患者年齡超過70歲，他們經常不像年輕病患一樣接受同樣的照護。
　　
　　Haller醫師於2010年腸胃癌症研討會的新聞簡報中發表他的發現。該年會由美國腸胃醫學會、美國臨床腫瘤醫學會（ASCO）、美國放射腫瘤學學會以及腫瘤外科醫學會贊助。
　　
　　他表示，使用較新的化學治療藥物作為罹患第三期大腸癌老年病患的輔助治療仍是個有爭議的議題，且這些發現與最近兩項研究相反。一項發表於ASCO 2009年的ACCENT資料庫分析結果（McCleary NAJ等人；Abstract 4010）發現70歲以上老年病患，使用較新的oxaliplatin或是capecitabine為主的療程，相較於5-FU/LV，並沒有額外的好處。同樣的，最近發表的一項研究，MOSAIC試驗（J Clin Oncol 2009;27:3109-3116），以oxaliplatin以及5FU/LV治療對於老年病患並無法提供更多好處。
　　
　　他指出，這些數據已經促使臨床醫師們決定不對他們的老年病患使用這些藥物。除此之外，根據這些研究結果，德國臨床治療指引重新更新，且至少一項歐洲研究修改計畫書排除70歲以上老年病患。他向記者們表示，我們覺得需要檢視我們的XELOX資料庫，確認老年族群病患在我們的研究中是否受益。
　　
　　這項研究收納1,886位罹患第三期大腸癌患者，這些病患在手術後被隨機分派接受XELOX或5-FU/LV。在平均追蹤57個月後，分析3年免於疾病存活率發現XELOX的效果在年輕與高齡族群相當。
　　
　　Haller醫師表示，整體來說，XELOX組免於疾病存活率為71%，5-FU/LV組則是67%，兩組間的差異達統計上顯著水準。年齡低於70歲的病患們（共有1,477位）接受XELOX治療的3年存活率為72%，接受標準療程的則是69%（危險比值[HR]為0.79；95%信賴區間[CI]為0.66-0.94）。Haller醫師指出，那些70歲以上的病患（共409位），免於疾病存活率分別為66%與60%（HR為0.87；95% CI為0.63-1.18）。
　　
　　在回應記者的回應時，Haller醫師承認老年病患的信賴區間跨過1.0，因而缺乏統計上顯著差異。他解釋，我們看的是趨勢。在年齡超過70歲的次組中，人數下降至400位，每組僅有200人，因此會影響危險比值。
　　
　　然而，Haller醫師相信這些數據足以挑戰MOSAIC研究發現。雖然NO16968是使用輔助化學治療最大的研究之一，他指出MOSAIC僅針對1,200位病患進行，且大部分是低風險的第二期病患，這致使因化學治療帶來的好處令人質疑。
　　
　　他附帶表示，他預期會有相當激烈的爭辯。我的擔憂是，以去年於ASCO舉辦的10分鐘發表會，醫師們回到執業場所後停止使用XELOX治療70歲出頭的病患。
　　
　　我們的結論是，除了其他兩種5-FU/oxaliplatin療程外，XELOX是新的標準照護，不論年齡。以口服capecitabine，治療變得更加方便，讓病患就診次數降到最低，且不需要使用外科植入裝置與使用輸液幫浦。
　　
　　記者會引言人、格蘭福克北達科他醫學院與健康科學外科教授Robert Sticca醫師稱這項發現為我們目前已知老年病患對輔助療程之外重要的資訊。他附帶表示，這是有說服力的，這項研究的數字令人印象深刻。
　　
　　Haller醫師表示與Sanofi-Aventis與Hoffmann-La Roche公司有合作關係。Sticca醫師表示已無相關資金上的往來。


Oxaliplatin Improves Outcomes in Elderly With Colorectal Cancer

By Caroline Helwick
Medscape Medical News

January 22 (Orlando, Florida) — In contrast to some previous studies that found no benefit with newer chemotherapy regimens in elderly colorectal cancer patients, a randomized phase?3 trial showed better outcomes with adjuvant capecitabine and oxaliplatin (XELOX) than with standard 5-fluorouracil and leucovorin (5-FU/LV). The results came from a subanalysis of the NO16968 study, which compared adjuvant XELOX with standard chemotherapy in stage?III patients.

"Half of all newly diagnosed colon cancer patients are over 70 years old and they are frequently not offered the same care as younger patients," said Daniel G. Haller, MD, the Deenie Greitzer Professor of Gastrointestinal Oncology at the University of Pennsylvania's Abramson Cancer Center in Philadelphia.

He presented his findings here at a press briefing as part of the 2010 Gastrointestinal Cancers Symposium. The annual meeting is cosponsored by the American Gastroenterological Association, the American Society of Clinical Oncology (ASCO), the American Society for Radiation Oncology, and the Society of Surgical Oncology.

"The use of newer chemotherapy drugs in the adjuvant setting for older patients with stage?III colon cancer has been a topic of controversy, and these findings contradict conclusions from 2 recent studies," he noted. An analysis of the ACCENT database presented at ASCO?2009 (McCleary NAJ et al: Abstract 4010) found no additional benefit with newer oxaliplatin- or capecitabine-based regimens over 5-FU/LV in patients 70 years and older. Similarly, in the recently reported MOSAIC trial (J Clin Oncol 2009;27:3109-3116), adjuvant treatment with oxaliplatin and 5FU/LV did not offer additional benefits in elderly patients, he said.

"These data have prompted some clinicians to decide against using these drugs for their older patients," he said. In addition, on the basis of these studies, German clinical guidelines were revised, and at least 1 European trial was amended to exclude patients older than 70 years, he said. "We felt the need to mine our XELOX database to see if the elderly subgroup benefited in our study," he told journalists.

The study consisted of 1886 patients with stage?III colon cancer who were randomly assigned to receive XELOX or 5-FU/LV after surgery. After a median follow-up of 57 months, analysis of 3-year disease-free survival found the effectiveness of XELOX to be similar for both the younger and older age groups.

Overall, 3-year disease-free survival was 71% for the XELOX group and 67% for the 5-FU/LV group, a difference that was statistically significant, Dr. Haller said. Patients younger than 70 years of age (n?= 1477) receiving XELOX had a 3-year disease-free survival of 72%, compared with 69% for those receiving the standard regimen (hazard ratio [HR] 0.79; 95% confidence interval [CI], 0.66?- 0.94). For those 70 years or older (n?= 409), disease-free survival was 66% and 60%, respectively (HR, 0.87; 95% CI, 0.63?- 1.18), Dr. Haller reported.

In response to a journalist's question, Dr. Haller acknowledged that the confidence intervals crossed 1.0 for the elderly patients and therefore lacked statistical significance. "What we were looking at were trends," he explained. "In the subgroup over 70, we were down to 400 patients, only 200 per arm, so this affects the hazard ratio."

Nevertheless, Dr. Haller believes the data are strong enough to "challenge" the MOSAIC findings. Although NO16968 is one of largest trials in the adjuvant setting, he pointed out that MOSAIC looked at only about 1200 patients and had a larger proportion of low-risk stage?II patients, who derive questionable benefit from any chemotherapy.

He added that he anticipates a "vigorous debate" over the findings. "My concern is that, based on one 10-minute presentation at ASCO last year, physicians went back to their practices and stopped treating patients in their early 70s [with XELOX]."

"We conclude that, in addition to 2 other 5-FU/oxaliplatin regimens, XELOX is a new standard of care, regardless of age," he said. "With the oral capecitabine, treatment is more convenient, requires the fewest physician visits of any combination, and spares the patient the need for a surgically implanted access device and infusion pump."

Press briefing moderator Robert Sticca, MD, professor of surgery at North Dakota School of Medicine and Health Sciences in Grand Forks, called the findings "an important addition to our current knowledge" about adjuvant regimens in elderly patients." He added: "This is convincing, as the numbers in the study are very impressive."

Dr. Haller reports relationships with Sanofi-Aventis and Hoffmann-La Roche. Dr. Sticca has disclosed no relevant financial relationships.

2010 Gastrointestinal Cancers Symposium (GICS): Abstract?284. Presented January?22-25, 2010.