作者：Zosia Chustecka
出處：WebMD醫學新聞

July 6, 2006 – 一個英國研究團體於7月6日版新英格蘭醫學期刊提出Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC)試驗研究結果，指出在局部胃癌手術前後加上一個化療處方，顯著地比單只有進行手術改善了存活率。

聖文森特癌症綜合中心的John Macdonald醫師在編輯小語中指出，該試驗有說服力的介紹了手術前後的化療的好處，提供局部的、可切除的胃癌一個新治療選擇；此試驗設計良好、執行良好，且使醫師可在此堅定證據下有充分信心。

【顯著改善存活】
此MAGIC試驗由英國倫敦的皇家麥斯登醫院的David Cunningham醫師主導，收納超過500位可切除的胃腺癌、胃食道連結處腺癌、或下食道腺癌的病患；這些病患隨機接受僅有手術治療或在手術前後併用化療；平均追蹤期4年之後，手術組的253位病患中的170位死亡，手術前後併用化療組的250位病患則有149位死亡。

手術前後併用化療組的5年存活率是36%，僅有手術組的5年存活率是23%；因此，研究者認為5年存活率改善估計達13%，相對的可以降低25%的死亡風險。

此外，手術前後併用化療組的整體存活率(死亡HR， 0.75；P = .009) 以及無惡化存活率(惡化HR，0.66；P < .001)均有較高的可能性。

【化療處方可能可以修改】
MAGIC試驗使用的化療處方組成是epirubicin、cisplatin和fluorouracil (ECF)，在術前3個循環以及術後3個循環；試驗中所用的epirubicin的費用由Pharmacia公司補助，除此之外係由英國醫療研究會議所贊助。

此ECF處方係於1980年代晚期所發展，現在有更新且較不複雜的處方，有些已試用於此類病患，舉例來說， capecitabine取代fluorouracil 以及oxaliplatin取代cisplatin。

Macdonald醫師在編輯小語表示，無疑地，對使用何種藥物的爭論仍會持續，但是比化療處方內容更重要的是，手術前後的化療是否是改善可切除的胃腺癌治癒率的最佳方法。

Macdonald醫師指出，部分答案決定於當醫師第一次看見病患時；這是病患進行胃切除術之前的一個合理選擇，但是對那些已經進行手術者來說顯然不再是個選項；他指出，目前腫瘤醫師都是在病患進行治療目的之胃切除術後才看到病患。

Macdonald醫師向Medscape表示，有關Cunningham研究的最重要的一點，是提供醫師們一個有說服力的證據，證明手術前後使用化療可以幫助避免癌症復發和改善整體存活率；此研究給了醫師們處置可切除的胃癌病患時另一個有用的選擇 (在術後放射線治療和化療之外)。

【術前化療顯示可以縮小腫瘤】
手術前使用化療顯示可以有腫瘤縮小的結果；手術前後併用化療組的腫瘤尺寸顯著地縮小，平均最大直徑是3公分，僅有手術組的是5公分 (P = .001)。

MAGIC試驗的研究者之一、Yu Jo Chua表示，之前的胃癌手術後進行化療的試驗顯示並無提升存活率之好處，然而，不可能據此即結論認為術前化療也不會有所差異；Chua先生向Medscape解釋，此試驗的病患和其他如INT-0116試驗的病患之間的處理方式和時間點均有所不同，所以這些組別之間是無法比較的。

Chua先生預期，此試驗結果會引導改變某些醫學中心的臨床實務，特別是英國和歐洲；然而，也將受地區轉診模式、或如編輯所說的腫瘤科醫師第一次見到病患的時間等因素影響；Chua先生認為，理想的話，應該將腫瘤科醫師在診斷時納入決定治療計畫。


New Option in Gastric Cancer: Perioperative Chemotherapy Improves Survival

By Zosia Chustecka
Medscape Medical News

July 6, 2006 – Adding a regimen of chemotherapy before and after surgery for localized gastric cancer significantly improved survival compared with surgery alone, concludes a group of UK researchers reporting results from the Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC) trial in the July 6 issue of the New England Journal of Medicine.

This trial convincingly demonstrates a benefit from perioperative chemotherapy added to surgery and offers "a new option for the treatment of localized, resectable gastric cancer," says John Macdonald, MD, from St Vincents Comprehensive Cancer Center, New York, in an accompanying editorial. This trial was well designed and well executed and "clinicians can have confidence in the solid evidence," he adds.

Significantly Improved Survival

The MAGIC trial, headed by David Cunningham, MD, from the Royal Marsden Hospital, London, United Kingdom, was conducted in more than 500 patients with resectable adenocarcinoma of the stomach, esophageal junction, or lower esophagus. Patients were randomized to treatment with surgery alone or to surgery combined with perioperative chemotherapy. After a median follow-up of 4 years, 170 of 253 patients in the surgery group had died, compared with 149 of 250 patients treated with surgery and chemotherapy.

The 5-year survival was 36% in the group that received chemotherapy compared with 23% in the group treated with surgery alone. Thus, 5-year survival was improved by an estimated 13%, which corresponds to a 25% reduction in the risk of death, the researchers comment.

In addition, the group treated with both modalities had a higher likelihood of overall survival (hazard ratio [HR] for death, 0.75; P = .009) and of progression-free survival (HR for progression, 0.66; P < .001).

Chemotherapy Regimen May Be Altered

The MAGIC trial used a chemotherapy regimen consisting of epirubicin, cisplatin, and fluorouracil (ECF), administered for 3 cycles preoperatively and 3 cycles postoperatively. The cost of epirubicin used in the trial was reimbursed by Pharmacia, but otherwise the trial was supported by the UK Medical Research Council.

This ECF regimen was developed during the late 1980s, and there are now newer and less complex regimens available, the researchers comment. Some are currently being tested in this patient population — for instance, capecitabine in place of fluorouracil and oxaliplatin in place of cisplatin.

No doubt the debate over which drugs to use will continue for some time yet, Dr. Macdonald comments in the editorial. But more important than the details of the chemotherapy regimen, he says, is the larger question of whether perioperative chemotherapy is the best way to improve the cure rate in resectable gastric adenocarcinoma.

Part of the answer hinges on when clinicians first see the patients, Dr. Macdonald writes. It is a reasonable option for patients seen before gastrectomy, but obviously it is no longer an option for those who have already undergone surgery. Yet it is not unusual for an oncologist to see such patients only after a gastrectomy with a curative intent has already been performed, he points out.

"The most important point about the Cunningham study is that it provides convincing evidence to clinicians that the use of perioperative chemotherapy can help prevent cancer recurrence and improve overall survival," Dr. Macdonald told Medscape. "This study gives clinicians another useful alternative (along with postoperative radiation and chemotherapy) in managing patients with resectable stomach cancer."

Preoperative Chemo Appears to Shrink Tumors

The use of chemotherapy before surgery appears to have resulted in tumor shrinkage; the tumors in the combined-modality group were significantly smaller, with a median maximal diameter of 3 cm compared with 5 cm in the other group (P = .001).

Previous trials in gastric cancer that evaluated adjuvant chemotherapy administered after surgery have not shown a survival benefit. However, it is not possible to conclude that it is the preoperative chemotherapy that made the difference in the observed outcome, said Yu Jo Chua, an investigator in the MAGIC trial and a research fellow from the Royal Marsden Hospital working with Dr. Cunningham. The patients in this trial and those participating in adjuvant trials, such as the INT-0116 trial, were enrolled at different time points in their management pathway, and so the groups are not comparable, Mr. Chua explained to Medscape.

"The results of this trial will lead to a change in clinical practice in<