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作者：Nick Mulcahy  
出處：WebMD醫學新聞

　　November 5, 2009 (芝加哥) — 適用於治療心血管疾病的抗凝血劑，對於前列腺癌可能也有所幫助。
　　
　　根據一篇對662名男性進行的回溯研究，包括阿斯匹靈、warfarin與clopidogrel等抗凝血劑，可以改善接受放射線治療之局部前列腺癌男性病患的生化控制。
　　
　　該研究的第一作者在美國放射腫瘤協會第51屆年會發表壁報時表示，高風險局部病灶的病患獲得的潛在幫助最大。
　　
　　伊利諾州芝加哥大學Pritzker醫學院的Kevin S. Choe博士解釋，目前的研究僅針對接受放射線治療的前列腺癌男性，而非以手術治療者。
　　
　　Choe博士報告指出，接受放射線治療的這些男性病患服用抗凝血劑所獲得的好處，是源自放射線與這些藥物的交互作用。
　　
　　四年時，採用前列腺特異抗原檢測測量生化控制，或稱為無生化復發，接受放射線治療且服用抗凝血劑的前列腺癌病患組，統計上顯著優於未接受此類薄血治療者(91% vs 78%；P= .0002)。
　　
　　Choe博士表示，我們還需要更多資料才可以建議接受放射線治療的男性考慮服用抗凝血劑。不過，擔任芝加哥大學放射腫瘤科住院醫師的這位年輕研究者，對於研究結果依舊做出正面的詮釋。已經使用抗凝血劑控制心血管疾病的局部前列腺癌男性，當他們接受放射線治療時會獲得額外助益。
　　
　　接受Medscape Oncology邀請發表評論的一名癌症與抗凝血劑專家相信，使用這些製劑在腫瘤科方面有其可考量之處。White River Junction VA醫學中心、丹佛Dartmouth醫學院的Leo R. Zacharski醫師表示，那相當值得進行，花費低又有效。
　　
　　Zacharski醫師表示，這是此一議題上相當重要的一篇文獻，引用抗凝血劑對於小細胞肺癌的戲劇性效果為例，就怕太少人知道這篇文獻。
　　
　　Zacharski醫師對於目前的發現有一論點。他表示，就我看來，最可能的解釋是，服用抗凝血劑的人失血會略為增加，而減少了體內的鐵含量。
　　
　　在一篇有關周邊動脈疾病且鐵減少之男性病患的隨機試驗中，Zacharski醫師等人發現，新癌症診斷與癌症相關死亡率在統計上顯著減少(J Natl Cancer Inst. 2008;14:996-1002)。他表示，這效果在前列腺癌和其他癌症看來是一樣的。
　　
　　目前的這篇研究，是Choe博士等人研究直腸出血的另一篇前列腺癌病患研究的附加研究。他表示，以放射線治療的前列腺癌病患，服用抗凝血劑時，相較於未服用抗凝血劑的病患，有顯著較高的出血風險。
　　
　　因為此一併發症，當建議這類男性病患使用抗凝血劑時，Choe博士表示，必須謹慎計畫。
　　
　　【次組分析：只有高風險男性有顯著利益】
　　Choe博士指出，新研究著眼於局部前列腺癌男性。Zacharski醫師認為這是適當的，已確立的前列腺癌對於抗凝血劑沒有反應。
　　
　　該研究世代包括662名前列腺癌病患，於1988至2005年間在芝加哥大學接受放射線治療。這些男性中，243人曾接受warfarin、clopidogrel和/或阿斯匹靈。多數男性僅單用阿斯匹靈(n= 161人)、或只單用warfarin(n= 42人)。
　　
　　這些男性以組織內放置射線元素和/或體外放射線照射治療。Choe博士表示，接受的放射線類型並不會影響生化控制結果。約半數男性也接受短期的雄性素去除療法。
　　
　　根據國家綜合癌症網絡準則，在這243名病患中，低風險的有38%、中度風險的有38%、高風險的有25%。
　　
　　次組分析中，相較於未曾服用這些藥物的低風險與中度風險男性，服用抗凝血劑的低風險與中度風險男性，其生化控制有明顯改善。
　　
　　不過，只有高風險男性(n= 165人)的生化控制有統計上的顯著改善。這一小組中，服用抗凝血劑的男性(n= 52人)，4年時無生化復發(即所謂的生化控制)比率為82.4%，未服用抗凝血劑組為57.6%(n= 113人；P= .0007)。
　　
　　Choe博士表示，看來生化控制的助益在局部高風險男性最大。
　　
　　該研究也指出抗凝血劑的其他利益：這些藥物與降低轉移比率有關。
　　
　　服用抗凝血劑組的4年時遠端轉移比率低於未服用抗凝血劑組(1% vs 5%；P= .0248)。Choe博士表示，抗凝血劑可能會抑制腫瘤的擴散能力，這些結果可能為此假設提供臨床前證據。
　　
　　Choe博士與 Zacharski醫師皆宣告沒有相關財務關係。
　　
　　美國放射腫瘤協會(ASTRO)第51屆年會：摘要2269。發表於2009年11月2日。

Anticoagulants May Aid Biochemical Control in Prostate Cancer

By Nick Mulcahy
Medscape Medical News

November 5, 2009 (Chicago, Illinois) — Anticoagulants are indicated for the treatment of cardiovascular disease but might have a role to play in prostate cancer.

Anticoagulants, including aspirin, warfarin, and clopidogrel, were associated with improved biochemical control of localized prostate cancer in men treated with radiation therapy, according to a new retrospective study of 662 men.

The potential benefit is most pronounced in patients with high-risk localized disease, according to the study's lead author, who presented a poster here at the American Society for Radiation Oncology 51st Annual Meeting.

The current study looked only at men with prostate cancer treated with radiation, not with surgery, explained Kevin S. Choe, MD, PhD, from the University of Chicago Pritzker School of Medicine in Illinois.

The benefit seen in men who undergo radiotherapy while taking anticoagulants likely stems from an "interaction" between the radiation and the drugs, reported Dr. Choe.

At 4 years, biochemical control, or the absence of biochemical relapse as measured by prostate-specific antigen testing, was statistically significantly better in the group of prostate cancer radiotherapy patients receiving anticoagulants than in the group not receiving the blood-thinning therapy (91% vs 78%; P?= .0002).

"We need more data before recommending that men undergoing radiotherapy consider taking anticoagulants," said Dr. Choe. However, the young investigator, who is a resident in radiation oncology at the University of Chicago, also put a positive spin on the results. "Those men with localized prostate cancer who already are on anticoagulants for cardiovascular disease may receive additional benefit when they undergo radiotherapy."

It would need to be planned out very carefully.

The current study was an outgrowth of another study in these same patients, in which Dr. Choe and colleagues investigated rectal bleeding. Prostate cancer patients treated with radiotherapy while taking anticoagulants had a significantly higher risk for this bleeding than patients not taking anticoagulants, he said.

Given this complication, if anticoagulants were ever to be recommended for use in these men, "it would need to be planned out very carefully," said Dr. Choe

Subgroup Analysis: Benefit Only Significant in High-Risk Men

Preclinical studies have indicated that anticoagulants have antineoplastic properties, said Dr. Choe. However, numerous phase?3 randomized studies in a variety of cancer patients, including those with prostate cancer, have failed to show that anticoagulants, as a group, provide therapeutic benefit. Those studies were in patients with advanced disease, said Dr. Choe; the new study is the first in men with localized prostate cancer.

The study cohort consisted of 662 patients with prostate cancer who were treated with radiotherapy at the University of Chicago from 1988 to 2005. Of these men, 243 were receiving warfarin, clopidogrel, and/or aspirin. Most of the men were receiving aspirin alone (n?= 161) or warfarin alone (n?= 42).

The men were treated with seed implants and/or external-beam radiation. The type of radiation received did not influence biochemical control outcomes, said Dr. Choe. About half the men also received short-term androgen-deprivation therapy.

Among the 243 patients, risk was low in 38%, intermediate in 38%, and high in 25%, according to National Comprehensive Cancer Network criteria.

In a subgroup analysis, the improvement in biochemical control was apparent among low- and intermediate-risk men taking anticoagulants, compared with the respective risk groups of men not taking the drugs.

However, biochemical control was only statistically significant in the high-risk men (n?= 165). In that subgroup, the men taking anticoagulants (n?= 52) had a 4-year rate of freedom from biochemical recurrence (i.e., biochemical control) of 82.4%, compared with 57.6% of those not taking anticoagulants (n?= 113; P?= .0007).

The benefit of biochemical control appears to be most pronounced in men with localized high-risk disease.

"The benefit of biochemical control appears to be most pronounced in men with localized high-risk disease," said Dr. Choe.

Anticoagulants had another benefit in the study: the drugs were associated with a reduced rate of metastasis.

The distant metastasis rate at 4 years was lower in the group taking anticoagulants than in the group not taking anticoagulants (1% vs 5%; P?= .0248). "Anticoagulants may inhibit a tumor's ability to spread," said Dr. Choe, adding that "mounting preclinical evidence" supports this hypothesis.

Dr. Choe has disclosed no relevant financial relationships.

American Society for Radiation Oncology (ASTRO) 51st Annual Meeting: Abstract 2269. Presented November 2, 2009.