使用阿斯匹靈可降低Lynch氏症候群的大腸直腸癌風險
作者：Roxanne Nelson
出處：WebMD醫學新聞
September 22, 2009 (德國柏林) — 根據發表於第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的研究，每天使用一次阿斯匹靈，可以為Lynch氏症候群患者提供防止大腸直腸癌的保護力，且保護力持續到停用阿斯匹靈之後數年。
阿斯匹靈也可降低此類病患子宮內膜癌的風險。
第一作者、英國Newcastle大學人類基因研究中心主任John Burn醫師表示，結果相當令人振奮，我們在停止給予阿斯匹靈之後4年還看到有效；在該試驗中，使用阿斯匹靈的期間有直接關聯。
【獲得的長期效果】
阿斯匹靈的化學預防效果無法立即看見。此研究的初步結果在去年發表(N Engl J Med. 2008;359:2567-2578)， 當時Burn醫師指出，頗令人失望，因為在隨機分組之後平均29個月時，腫瘤生成方面並無差異。服用阿斯匹靈者與服用安慰劑者的大腸直腸癌比率相當。
不過，研究者指出，曾經參與稍早阿斯匹靈之心血管試驗的人，在10年後的大腸直腸癌案例較少。Burn醫師表示，這是我們持續嘗試的動力。
最初的試驗隨機分組之後大約5年，阿斯匹靈組和安慰劑組新發生惡性腫瘤的發生率開始有所不同，阿斯匹靈使用者的大腸直腸癌案例數減少。研究者指出，阿斯匹靈的保護效果，在最後一次使用阿斯匹靈之後6年都還持續存在，在本研究中，此效果和使用阿斯匹靈期間有關聯。
原本的研究中，研究對象是1,071名Lynch氏症候群，也稱為遺傳性非瘜肉性大腸直腸癌的患者，隨機分組接受每天600 mg的阿斯匹靈和/或30 g的Novelose，這是一種無法在小腸消化的抗性澱粉。
Burn醫師指出，即便案例控制研究與流行病學研究報告皆顯示，使用非類固醇抗發炎藥物可減少大腸直腸癌風險，隨機控制試驗卻無法顯示此一效果。
他表示，我們決定採取一種不同的方法、探究Lynch氏症候群；我們將之視為適合化學預防研究的一組，因為這些人相當積極。
【無法預防腺瘤，出血事件很少】
Burn醫師強調，本研究中，目標不是預防腺瘤而是預防癌症。大約有100名研究對象發生腺瘤，但是並未發展成癌症。他表示，我們無法預防腺瘤發生，但是我們避免了腺瘤變成惡性。
迄今為止，研究者在使用阿斯匹靈的研究對象中只有觀察到6例大腸癌，安慰劑組有16例。有6人也發生多發大腸直腸癌，其中有服用阿斯匹靈的只有1人。
儘管使用高劑量阿斯匹靈，出血也不是問題，阿斯匹靈組中，11人發生值得注意的胃腸道出血，安慰劑組有9人發生。阿斯匹靈組的心血管事件比率也較低。
【推斷資料】
目前還不清楚要有多少這類資料才可以外推到其他族群。Burn醫師表示，所有大腸癌患者中，約有六分之一有某種的基因異常。因此可以說，如果可以預防此疾病遺傳類型的癌症，或許對其他疾病類型也有用。
不過，ESMO理事長、Jose Baselga醫師不確定在其他病患族群是否可以有相似的結果。他向Medscape Oncology表示，我不確定其他類型的大腸直腸癌也有不錯的反應，長追蹤期間的確是個相當久的過程。
英國的醫學研究委員會以及癌症研究支持本研究。
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6000。發表於2009年9月21日。
Aspirin Use Reduces Risk for Colorectal Cancer in Lynch Syndrome
By Roxanne Nelson
Medscape Medical News
September 22, 2009 (Berlin, Germany) — Using aspirin on a daily basis offers protection against colorectal cancer in individuals with Lynch syndrome, and that protection continues for years even after aspirin is discontinued, according to research presented here at the 15th Congress of the European CanCer Organization and the 34th European Society for Medical Oncology Multidisciplinary Congress.
Aspirin also reduced the risk for endometrial cancer in this population.
The results were particularly exciting, said lead author John Burn, MD, medical director and head of the Institute of Human Genetics, Newcastle University, Newcastle upon Tyne, United Kingdom. "We stopped giving the aspirin after 4 years and yet the effect is continuing. It is directly correlated with the duration of aspirin use in the trial."
Results Seen Over Long Term
The chemopreventive effect of aspirin was not seen immediately. The initial results of the study were published last year (N Engl J Med. 2008;359:2567-2578), and Dr. Burn noted that they were "profoundly disappointing," because there was no difference in neoplasia at an average of 29 months after randomization. The rate of colorectal cancer was similar in those taking aspirin and those taking placebo.
However, the researchers noted that individuals who had participated in early cardiovascular trials with aspirin had fewer cases of colorectal cancer after 10 years. That was an impetus for "us to keep trying," Dr. Burn said.
About 5 years after initial trial randomization, the incidence of new malignancies in the aspirin and placebo groups began to diverge, and the number of cases of colorectal cancer in aspirin users declined. The protective effect of aspirin appeared to persist for at least 6 years after the last episode of aspirin use, and also correlated with the duration of aspirin use during the study, the researchers note.
In the original study, 1071 people with Lynch syndrome, also known as hereditary nonpolyposis colorectal cancer, were randomized to 600?mg of aspirin per day and/or 30?g of Novelose, a resistant starch that escapes digestion in the small intestine.
Dr. Burn pointed out that even though case–control and epidemiologic studies have reported that the use of nonsteroidal anti-inflammatory drugs decreases the risk for colorectal cancer, randomized controlled trials have failed to show this effect.
"We decided to take a different approach and look at Lynch syndrome," he said. "We thought it was an interesting group for a chemoprevention study, since these people are very motivated."
Adenomas Not Prevented, Bleeding Incidents Minimal
Dr. Burn emphasized that, in this study, the goal was not to prevent adenomas but to prevent cancer. About 100 study participants developed adenomas, but there was no propensity to develop cancer. "We didn't prevent the adenomas from occurring, but we prevented adenomas from becoming malignant," he said.
To date, the researchers have observed only 6 cases of colon cancer among the study participants who used aspirin, compared with 16 cases in the placebo group. Six individuals also developed multiple colorectal cancers and, of this group, only 1 was taking aspirin.
Bleeding was also not an issue, despite the high dose of aspirin. In the aspirin group, 11 participants experienced notable gastrointestinal bleeding, as did 9 in the placebo group. Individuals in the aspirin group also had a lower rate of cardiovascular events.
Extrapolating the Data
It is currently unclear how much of these data can be extrapolated to other populations. "About 1 in 6 of all colon cancers has some type of breakdown in this gene system," said Dr. Burn. "So one might say that if it prevents cancer in the inherited form of the disease, it might work well in other forms of the disease."
However, Jose Baselga, MD, president of ESMO, is not certain that similar results will be experienced in other patient groups. "I'm not sure that other types of colorectal cancer will respond as well," he told Medscape Oncology. "It does seem to be a very long process with a long follow-up time."
The study was funded by the Medical Research Council in the United Kingdom and by Cancer Research UK.
15th Congress of the European CanCer Organization (ECCO 15) and the 34th European Society for Medical Oncology (34th ESMO) Multidisciplinary Congress: Abstract 6000. Presented September 21, 2009.
