[Health]WebMD醫學新聞-預防前列腺癌成真

預防前列腺癌成真

作者：Roxanne Nelson
出處：WebMD醫學新聞

September 25, 2007 — 前列腺癌是西方國家中男性主要致死癌症，風險因素如年紀、種族以及家族史均無法控制，但是有越來越多的資料顯示此病可能是可以預防的；在9月24日的癌症期刊（Cancer）線上版中，多倫多大學的Neil Fleshner醫師和Alexandre Zlotta醫師發表的一篇回顧文獻，討論此病的可能預防策略，以及需要發展的分子學方法 ，以證明導致前列腺細胞惡化的過程。
　　
　　Fleshner醫師向Medscape Oncology表示，一直以來，我們對前列腺癌已經知道頗多，現在所證明的是使用finasteride的經驗，認為某些程度的前列腺癌是可以預防的疾病；值得注意的是，此一發現在10年前並不存在，而是現在才發現；一開始的流行病學觀察報告已經變成防止攝擭腺癌的尖端學問上許多可信的科學。
　　
　　Fleshner醫師指出，預防癌症比儘早發現和治療好，我認為，大多數的人會同意有效預防此病的方法比找出癌症並加以摧毀還更有用。
　　
　　前列腺癌是男性最常見的惡性疾病，在某些方面，看似自然老化過程中的一部份現象；驗屍解剖發現，當男性進入40歲之後，有三分之一已經發生惡性前列腺腫瘤，到了將近60歲，估計將近60%的男性中可以發現有這些小腫瘤，解剖驗屍時的這些隱性癌症（occult cancers）的比率在全球似乎是相同的，然而，前列腺癌相關死亡率卻有所不同。
　　
　　Fleshner醫師解釋，因前列腺癌而死的整體風險仍相當低，男性前列腺癌病患的主要致死原因是心臟病，因為組織學證據和死亡率之間是如此的不一致，很可能有過度診斷和過度治療的高風險；以侵入式介入方式治療早期的疾病可以改善整體存活率，但是許多病患接受了不必要的治療，之後變成必須和副作用如性功能不佳和泌尿問題搏鬥。
　　
　　Fleshner醫師解釋，預防前列腺癌是此一領域中相當新的觀念，一直到20年前才有以預防為目標的臨床試驗；在未來的1到5年，有許多重要的臨床試驗將趨於成熟，如果有一個或更多的結果獲得證明，我們將邁入預防臨床預防領域。
　　
　　此篇報告中，Fleshner醫師和Zlotta醫師回顧了目前研究中的預防策略，最近的試驗聚焦在許多介入方式，包括減少脂肪攝取，補充維他命 D、E和硒，以及食用大豆、綠茶，以及富含蕃茄紅素的食物；他們也檢視藥物方面的介入策略，如環氧合酶抑制劑、抗雌激素以及5-alpha-還原酶抑制劑。
　　
　　臨床試驗檢視的藥物介入方式顯示， 5-alpha-還原酶抑制劑，如finasteride和dutasteride，以及選擇性雌激素受體調節劑toremifene，在切片結果均顯示減少了前列腺癌細胞數；舉例來說，發現dutasteride減少良性前列腺肥大病患的惡性切片數達50%。
　　
　　案例控制生態世代研究，持續顯示脂肪飲食與前列腺癌之間的關係；在預防前列腺癌的飲食補充研究中，也展現出一些成果；一篇隨機研究評估硒在預防前列腺癌的角色，在10年期間，使用硒補充品的病患的疾病發生率減少49%。
　　
　　ATBC(Alpha-Tocopherol Beta-Carotene)試驗中，19,000位芬蘭男性隨機使用維他命 E、 β胡蘿蔔素、以上兩者或安慰劑，以判斷這些維他命補充品是否可以預防肺癌，結果發現服用維他命E的男性有三分之一減少了前列腺癌風險的驚人結果，其他研究顯示維他命E可以減少抽菸者的前列腺癌風險。
　　
　　其他營養品如綠茶的效果，比較沒有那麼明顯；至於大豆和番茄紅素的效果的研究則正在進行中。
　　
　　Fleshner醫師表示，目前最有效的預防製劑是5-alpha-還原酶抑制劑，因為這是我們唯一證明有效的；我們目前還有評估dutasteride的大型試驗進行中，此試驗稱為「Reduction by Dutasteride of Prostate Cancer Events (REDUCE) 」，將會是迄今為止最有效的。
　　
　　Fleshner醫師表示，其他的藥物研究包括評估toremifene在預防高度前列腺上皮內腫瘤的效果；總而言之，這些研究的結果能對前列腺癌的治療模式有重要影響。
　　
　　Fleshner 醫師擁有 Bioadvantex Pharma的股權。
　　
　　發表於2007年9月27日的線上版癌症(Cancer)期刊。

Preventing Prostate Cancer Becoming a Reality

By Roxanne Nelson
Medscape Medical News

September 25, 2007 — Prostate cancer is a leading cause of cancer death among men in Western nations, and while risk factors such as age, race, and family history cannot be controlled, a growing body of data suggests that it may be a preventable disease. In a review paper published in online September 24 in Cancer, Neil Fleshner, MD, and Alexandre Zlotta, MD, PhD, both from the University of Toronto, in Ontario, discuss potential prevention strategies for the disease as well as the need to continue investigations into the molecular pathways that develop, sustain, and lead to the progression of malignant cells in the prostate.

"We are learning so much about prostate cancer all the time," Dr. Fleshner told Medscape Oncology. "We have proven now, with our experience with finasteride, that prostate cancer is a preventable disease on some level. What is remarkable about this field is that it didn’t exist 10 years ago, and now it has exploded. What started as epidemiological observations has moved into a body of credible science that is suggesting that we are on the cusp of being able to prevent prostate cancer."

Preventing cancer is preferable to early detection and treatment, Dr. Fleshner pointed out. "I think most everyone would agree that an effective way of preventing this disease is far more advantageous on a population level than searching out cancers and destroying them."

Prostate cancer is the most common malignancy found in males, and in some aspects, appears to be a part of the natural aging process. Autopsies have indicated that by the time men enter their fourth decade of life, about a third already have small malignant prostate tumors. By approximately age 60 years, these small carcinomas can be found in an estimated 60% of all men. The rates of these occult cancers at autopsy seem similar worldwide, despite the variation in prostate cancer–related mortality rates.

The overall risk of dying from prostate cancer remains quite low, and Dr. Fleshner explained that the major cause of death for men with prostate cancer is heart disease. With such a large discordance between histologic incidence and mortality, there is a high risk for overdetection and overtreatment. Aggressive interventions for early-stage disease have improved overall survival, but many patients receive unnecessary treatment and then must contend with adverse effects such as sexual dysfunction and urinary problems.

The whole concept of preventing prostate cancer is a relatively new field of study, Dr. Fleshner explained, and clinical trials aimed at prevention were not even contemplated until 2 decades ago. "We have several major clinical trials that will be maturing in the next 1 to 5 years, so we are on the cusp of moving preventive agents into the clinical area, assuming that 1 or more of the results will be positive."

In this paper, Drs. Fleshner and Zlotta review prevention strategies that are currently under study. Recent trials have focused on a number of interventions, including the use of dietary fat reduction and supplementation with vitamins D, E, and selenium, as well as consumption of soy, green tea, and food products rich in lycopene. They also examined preventive strategies using pharmacological agents such as cyclooxygenase inhibitors, antiestrogens, and 5-alpha-reductase inhibitors.

Clinical trials examining pharmaceutical interventions have shown that 5-alpha-reductase inhibitors such as finasteride and dutasteride, along with the selective estrogen-receptor modifier toremifene, have demonstrated promising results in decreasing the number of prostate cancers at biopsy. As an example, dutasteride was found to decrease the number of malignant biopsies among patients with benign prostatic hypertrophy by 50%.

Case-control, ecologic, and cohort studies have consistently demonstrated an association between dietary fat and prostate cancer. Studies investigating the use of dietary supplements in preventing prostate cancer have also shown promising results. A randomized study evaluating selenium's role in preventing prostate cancer found that, over a 10-year period, the incidence of the disease was reduced by 49% among the participants who used selenium supplements. A surprising result of the Alpha-Tocopherol Beta-Carotene (ATBC) trial, which randomized 19,000 Finnish men to vitamin E, beta-carotene, both, or placebo to determine whether certain vitamin supplements would prevent lung cancer, showed a one-third reduced chance of prostate cancer among men who took vitamin E. Other studies suggest that vitamin E may reduce the risk of prostate cancer among smokers.

The efficacy of other nutritional approaches, such as green tea, has been less clear, the researchers report. Studies evaluating the efficacy of soy and lycopene are ongoing.

"Right now, the most promising preventive agents are the 5-alpha-reductase inhibitors, only because we have proof that they work," said Dr. Fleshner. "We have a large trial under way right now that is evaluating dutasteride, called the Reduction by Dutasteride of Prostate Cancer Events (REDUCE), and that may be the most promising to date."

Another pharmacologic study is evaluating the efficacy of toremifene in preventing high-grade prostatic intraepithelial neoplasia. "Altogether, the results of these studies can have a major impact on the way prostate cancer is dealt with," said Dr. Fleshner

Dr. Fleshner owns shares in Bioadvantex Pharma.

Cancer. Published online September 24, 2007.