【24drs.com】February 1, 2010 — 美國心臟協會、美國癌症協會、美國泌尿科協會聯合發表的新建議聲明指出，雄性素去除療法(androgen-deprivation therapy，ADT)治療前列腺癌和心血管風險之間有關聯。
這些團體解釋，ADT是治療前列腺癌的主要療法之一，它顯示可以延長某些病患的存活，雖然有許多研究認為，接受ADT病患的心血管疾病和死亡風險增加，其他研究則未顯示有任何此類關聯。
該建議聲明指出，ADT和心血管事件之間的因果關係目前尚無法確定，作者們寫道，不過，這看似有理。
這篇建議聲明線上登載於2月1日的Circulation期刊。
作者們解釋，它的目的是純粹提供資訊，他們強調，這篇建議不應被解釋為支配臨床實務或者替代醫師們的臨床判斷，它也不應被用於法醫學方面的目的。
但是仍然有一些建議，包括了心臟科醫師、泌尿科醫師與腫瘤科醫師的撰寫小組表示，在以下幾點有達到共識：
* 對於被認為接受ADT有幫助的病患，沒有清楚的適應症，他們可以經由內科醫師、內分泌科醫師、或者心臟科醫師評估之後才開始使用ADT，或者他們接受特定的心臟檢測。
* 對於心臟病患、治療利益大過於可能風險的病患，是否開始使用ADT，最好是由治療前列腺癌的醫師決定比較適當。
* 接受ADT的病患應轉診給他們的一線照護醫師，進行定期追蹤評估ADT的可能代謝效果。
* 若適合的話，心臟病患應接受如同AHA建議的次級預防措施，包括降血脂治療、抗高血壓藥物、降血糖治療以及抗血小板治療。
ADT通常包括性腺激素釋放素(GnRH)致效劑，如leuprolide、goserelin以及triptorelin，不過，抗雄性素如flutamide以及bicalutamide也通常會被使用，併用GnRH 致效劑。
【許多新研究提倡】
有許多新研究提倡此一建議聲明，這些報告也指出，在使用ADT治療的前列腺癌病患中，心血管事件增加，包括心肌梗塞與心血管原因死亡(Keating NL 等人，J Clin Oncol. 2006;24:4448-4456; Saigal CS等人，Cancer. 2007;110:1493-1500; D'Amico AV等人，J Clin Oncol. 2007;25:2420-2425; Tsai HK等人，J Natl Cancer Inst 2007; 99:1516-1524; D'Amico Av等人，Cancer. 2008;113:3290-3297)。
工作小組指出，很可能因為這些報告，增加了內科醫師、內分泌科醫師以及心臟科醫師有關病患接受ADT的諮詢， 許多 醫師已經瞭解到潛在的問題。
第一作者、工作小組主席、德州休士頓Baylor醫學院醫學教授Glenn Levine醫師表示，這篇建議聲明之目標在填補資訊上的差距，讓一些聲明資訊連同資料而幫助醫師們在治療病患時有所指引。
他向Medscape Oncology表示，不過，在目前，有關ADT影響心血管風險因素的好資料有限，現有的資料無法被視為是確定的，我們相信，醫師應有所警覺。
Levine醫師表示，目前，心臟科醫師並不需要在開始使用ADT之前直接參與ADT病患的評估，Levine醫師本身也是一名心臟科醫師。他表示，醫師們處方ADT，不論是腫瘤科醫師、泌尿科醫師或者放射腫瘤，都不需要認為一定要將每個病患在開始使用ADT前轉診給心臟科醫師評估；處 方 醫師最好可以衡量ADT的助益和任何可能的副作用。
Levine醫師指出，如果接受ADT病患被轉診給一名心臟科醫師，目前沒有資料認為心臟科醫師必須進行壓力測試、導管或放置支架來重建血管。
Levine醫師接著表示，不過，因為ADT在許多病患看來似乎對心血管風險因素有影響，病患必須轉診給他們的一線照護醫師以進行監測，他們的一線照護醫師應對病患使用ADT有所警覺，這可以確保適當的預防照護，例如控制血脂與血壓，其他一般建議包括不要抽菸、不要過重、規律運動。對於沒有心血管事件的病患以及發生心血管事件後的次級預防，這些都是初級預防。
【相關的機轉還不清楚】
如果ADT真的會增加心血管風險，其機轉目前還不清楚。作者們在報告中指出，ADT的代謝效果包括增加體重、減少胰島素敏感度、和/或增加血清膽固醇與三酸甘油脂。他們也指出，代謝改變模式看起來和一般定義的代謝症候群有所不同。
Levine醫師表示，不過，是否有這些效果或者是其他機轉牽涉其中都需要被確認，或許有多重因素，在不同病患中有不同的機轉。
工作小組的18名作者中有多數宣告沒有相關財務關係，有3人報告擔任多家藥廠的顧問或諮詢委員，詳見於報告中。
Circulation. 線上發表於2010年2月1日。
Cardiovascular Risk With Androgen-Deprivation Therapy for Prostate Cancer
By Zosia Chustecka
Medscape Medical News
February 1, 2010 — "There may be a relationship" between androgen-deprivation therapy (ADT) for prostate cancer and cardiovascular risk, states a new advisory issued jointly by the American Heart Association (AHA), the American Cancer Society, and the American Urological Association.
ADT is a mainstay of treatment for prostate cancer, the group explains, and it has been shown to extend survival in certain patient populations. Although there have been several studies suggesting that patients receiving ADT have an increased risk for cardiovascular disease and mortality, other studies have not shown any such association.
A causal relation between ADT and cardiovascular events "cannot be determined definitely at this point," the advisory states. "However, it is plausible," the authors add.
The advisory was published online on February? 1 in Circulation.
Its purpose is "strictly informative," the authors explain. "This advisory should not be construed as dictating clinical practice or superseding the clinical judgment of physicians, and it should not be used for medicolegal purposes," they emphasize.
Nonetheless, there are a few recommendations. The writing group, which includes cardiologists, urologists, and oncologists, says that it reached a consensus on the following points:
· For patients in whom ADT is believed to be beneficial, there is no clear indication that they be referred for evaluation by internists, endocrinologists, or cardiologists prior to initiating ADT, or that they undergo specific cardiac testing.
· The decision of whether or not to initiate ADT in patients with cardiac disease, in whom the benefits of therapy would be weighed against any possible risks, is most appropriately made by the physician treating the patient for prostate cancer.
· Patients receiving ADT should be referred to their primary care physician for periodic follow-up evaluation of the potential metabolic effects of ADT.
· Patients with cardiac disease should receive secondary preventative measures, as recommended by the AHA, including, when appropriate, lipid-lowering therapy, antihypertensives, glucose-lowering therapy, and antiplatelet therapy.
ADT usually consists of treatment with a gonadotropin-releasing hormone (GnRH) agonist, such as leuprolide, goserelin, and triptorelin, although antiandrogens, such as flutamide and bicalutamide, are often used as well, in combination with the GnRH agonists.
Prompted by Several New Studies
The advisory was prompted by several new studies that reported an increase in cardiovascular events, including an increase in myocardial infarction and cardiovascular death, in prostate cancer patients who were being treated with ADT (Keating NL et al. J Clin Oncol. 2006;24:4448-4456; Saigal CS et al. Cancer. 2007;110:1493-1500; D'Amico AV et al. J Clin Oncol. 2007;25:2420-2425; Tsai HK et al. J Natl Cancer Inst 2007; 99:1516-1524; D'Amico Av et al. Cancer. 2008;113:3290-3297).
Most likely as a result of these reports, there has been an increase in internists, endocrinologists, and cardiologists being consulted about patients receiving ADT, the working group notes, adding that many of these physicians have been unaware of the potential problem.
"This advisory aims to fill that information gap and make some informed statements synthesizing the data to help guide clinicians as they treat patients," said lead author and chair of the working group, Glenn Levine MD, FAHA, professor of medicine at Baylor College of Medicine in Houston , Texas .
"There are fairly good data that ADT affects cardiovascular risk factors, although, at this time, the data cannot be considered to be definitive" he told Medscape Oncology. "We believe that physicians should be aware of it."
Currently, cardiologists do not need to be directly involved in the evaluation of patients for ADT prior to the initiation of ADT, said Dr. Levine, a cardiologist himself. "The physician prescribing the ADT, whether an oncologist, urologist, or radiation oncologist, does not need to feel obligated to refer every patient for cardiology evaluation before initiating ADT; it is the prescribing physician that is best placed to weigh the benefits of ADT against any potential side effects," he said.
If patients receiving ADT are referred to a cardiologist, there are currently no data to suggest that the cardiologist feel obligated to carry out a stress test, catheterization, or stent placement for revascularization, Dr. Levine added.
However, because ADT does seem, in many people, to have an impact on cardiovascular risk factors, patients should be referred to their primary care physicians for monitoring, and their primary care physicians should be made aware of the fact that the patient is receiving ADT, Dr. Levine continued. This should ensure optimal preventive care, such as controlling lipids and blood pressure, and more general advice to not smoking, not be overweight, and to exercise regularly. This is true for primary prevention in patients who have not had a cardiovascular event and for secondary prevention in patients after an event, he said.
Mechanisms Involved Are Unclear
The mechanism by which ADT might increase cardiovascular risk, if indeed it does, is unclear. In the paper, the authors note that ADT has metabolic effects that can include increasing body weight, reducing insulin sensitivity, and/or increasing serum cholesterol and triglyceride levels. They also point out that the pattern of metabolic alteration appears to be distinct from the classically defined metabolic syndrome.
However, whether it is these effects or some other mechanisms that are involved remains to be determined, Dr. Levine said. It might be that there are multifactorial effects, he continued, with different mechanisms involved in different patients.
Most of the 18 authors in the working group have disclosed no relevant financial relationships, but 3 report serving as consultants or advisory board members for various pharmaceutical companies, as detailed in the paper.
Circulation. Published online February 1, 2010.
作者：Zosia Chustecka
出處：WebMD醫學新聞
資料來源：國際厚生健康園區
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