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更新时间:2014-1-29 14:40:58 来源:华尔街日报中文网 作者:佚名

Custom-Fit Treatments for Prostate Cancer

In a bid to improve treatment for men with high-risk prostate cancer, some researchers want to take a page from the playbook for breast cancer.

Medical scientists are working to develop strategies for treating prostate tumors that are tailored to individual patients, as is currently done for many women with breast cancer. Fresh advances in the understanding of prostate cancer suggest that some men with a high-risk form of the disease might benefit from more aggressive treatment.

Other men may benefit from less treatment. For instance, radiation plus hormone therapy, also called androgen-deprivation therapy, is a common strategy to kill prostate tumors. But a recent study from researchers at Memorial Sloan-Kettering Cancer Center suggests that analyzing a tumor's DNA may identify patients who would do just as well with radiation alone. If borne out in further research, some men may be able to skip hormone therapy, avoiding side effects that include loss of libido and heart disease.

The developments come amid changes in the way many types of cancer are identified and treated. The changes are being driven in part by the use of genomic information that defines tumors by their underlying biology and provides clues about drivers of the disease not available by conventional exams.

Researchers say, for instance, that several new genomic prostate-cancer tests can help separate high-risk tumors from those at low or intermediate risk, offering information to doctors and patients to guide treatment choices.

About 240,000 men in the U.S. are diagnosed with prostate cancer each year. Most cases are low-risk forms of the disease that will have little effect on their lives or longevity. In these cases, a big concern is that overtreating the cancer puts these men at unnecessary risk for impotence, incontinence and other complications.

About 20% of diagnosed men are considered at high risk for having their cancers spread beyond the prostate gland based on a measure called the Gleason score and other factors. For some with an aggressive form of the disease, the 10-year-survival rate is well below 50%. 'We may not be treating them aggressively enough,' says William Polkinghorn, a radiation oncologist at Memorial Sloan-Kettering, in New York.

Some 95% of men who die of the disease are initially diagnosed with cancer that is confined to the prostate region, says Philip Kantoff, director of the Lank Center for genitourinary oncology at the Harvard-affiliated Dana-Farber Cancer Institute, in Boston. Finding ways to 'cure' such patients is 'mission central,' he says. Once cancer spreads beyond the prostate it is considered incurable.

The current standard of care for high-risk prostate cancer is either surgery to remove the cancerous gland or radiation plus hormone therapy to kill the tumor. Some men get radiation after surgery, but generally the two approaches aren't given together.

By comparison, women with high-risk breast cancer, which like prostate cancer is also typically fueled by sex hormones, typically get a combination of surgery, radiation and drugs. Medicines are tailored to patients based on whether the hormones estrogen and progesterone or a gene called HER2 is fueling the tumor.

Aggressive treatment of these women has resulted in improved survival and relapse rates, says Charles Sawyers, head of the human oncology and pathogenesis program at Memorial Sloan-Kettering. Whether a similar approach would improve survival for high-risk prostate cancer isn't certain but it is 'a conversation that needs to be had in a more vigorous way,' he says.

There is some evidence it could work. Research from clinical trials, for instance, suggests that giving radiation soon after surgery increases the time a patient lives without the disease coming back, says Adam Dicker, head of radiation oncology at Jefferson Medical College of Jefferson University, in Philadelphia.

But there have been few studies looking at the effect of combining treatments. It can take 10 to 15 years to complete a trial testing a multipronged strategy versus a single-treatment approach. 'People are hesitant to do those studies because they take such a long time to read out,' Dana-Farber's Dr. Kantoff said.

Genetic tests have recently become available that examine tumors for molecular signatures that predict whether a tumor is high- or low-risk and can help doctors make treatment decisions.

A test marketed by San Diego company GenomeDx Biosciences Inc. yields a molecular profile that can indicate, for instance, whether a man who undergoes prostate surgery to remove the tumor would also benefit from radiation treatment, says Doug Golginow, the company's chief executive.

It 'doesn't tell you if a specific chemotherapy' will work against the tumor, but 'it sorts out a lot of confusion by telling you whether you have the kind of disease that's going to kill you or not kill you,' he says.

Genomic Health Inc., in Redwood City, Calif., and Myriad Genetics Inc., of Salt Lake City, sell tests that, for instance, can help distinguish between high- and low-risk prostate cancers, possibly enabling men to delay or forgo aggressive treatment.

Dr. Polkinghorn's research at Sloan-Kettering yielded another genetic signature that could tell men when they need less therapy.

He led a recent study that showed androgen's role in prostate cancer goes beyond providing fuel for the tumor's growth; the male sex hormone also activates androgen receptors that turn on genes which repair damaged DNA. The finding is important because radiation kills tumor cells by breaking DNA. It also explains a two-decade-old mystery over why combining radiation with anti-androgen drugs is significantly more effective against high-risk cancer than radiation alone.

Depriving the tumor of androgen 'takes the sunscreen off the prostate cancer cell and makes it more sensitive to radiation,' Dr. Polkinghorn says. The report was published in November in the journal Cancer Discovery.

The analysis revealed levels of androgen-receptor activity vary widely among patients. This suggests patients with high androgen activity may benefit from hormone therapy while those with low activity levels may gain little from it and could forgo the treatment. The researchers aim to validate the result by testing it on a database of prostate-tumor specimens gathered from a variety of trials where the outcomes of the patients are known.

Dr. Polkinghorn now runs a clinic for high-risk prostate-cancer patients. He and his colleagues are developing a protocol to test how well such patients respond to more aggressive therapy.

Howard Bellin, a 77-year-old recently retired plastic surgeon who had surgery to remove his cancerous prostate in October, is being treated with the approach. The conventional approach, Dr. Bellin says, is for doctors to wait after surgery to see if the tumor comes back and then 'go after it with bigger guns' or hormone therapy. He says he is being treated now with two hormone drugs and radiation, hoping that a cure lies in 'treating it with your big guns right away.'



而对其他人来说,更少的治疗可以带来更好的疗效。举个例子,放射加激素疗法,也被称为“雄激素阻断治疗”是杀死前列腺肿瘤的常用方法,但纽约纪念斯隆-凯特琳癌症中心(Memorial Sloan - Kettering Cancer Center)研究人员近期的一项研究表明,通过分析肿瘤的DNA可以识别出哪些病人只用放射性治疗也能达到相同效果。若能经过进一步研究证实,则一些病人可能无需接受激素治疗,因此也可以避免性欲减少或心脏病等副作用。




根据格里森评分(Gleason score)及其他因素的一种检测,大概20%被诊断出前列腺癌的男性因其癌症已扩散至前列腺以外的部位而被认为具有高危风险。对于患有侵袭性肿瘤的人来说,10年的存活率远低于50%。纪念斯隆-凯特琳癌症中心的放射肿瘤学家威廉·波尔金霍恩(William Polkinghorn)称,可能我们的疗法还不够积极。

哈佛大学医学院附属丹娜-法伯癌症研究院(Dana-Farber Cancer Institute)位于波士顿,其兰克泌尿肿瘤中心 (Lank Center for genitourinary oncology) 主任菲利普·坎托夫(Philip Kantoff)表示,约95%因患此病而死的人最初诊断时肿瘤只限于前列腺部位。他说,找到办法治愈此类病人是“核心任务”。一旦肿瘤扩散到前列腺以外区域,则被认为无药可救。



纪念斯隆-凯特琳癌症中心人类肿瘤学和发病机制项目负责人查尔斯·索耶斯(Charles Sawyers)说,对女性患者的积极治疗令其存活率和复发率均有所改善。他说,类似方法是否能改善高危前列腺癌症的存活率还不能确定,但“两种癌症间的经验借鉴应该更加活跃”。

有证据显示类似方法是能起到作用的。费城托马斯·杰斐逊大学(Jefferson University)杰斐逊医学院(Jefferson Medical College)放射肿瘤系主任亚当·迪克尔(Adam Dicker)举例说,临床试验研究表明,接受手术之后不久就接受放射治疗增加了病人的寿命,同时减少了复发的可能。



例如, 地亚哥(San Diego)的公司GenomeDx Biosciences Inc.的首席执行官道格·哥尔基诺(Doug Golginow)表示,该公司推广的一项测试能检测出癌症分子特征,这些特征预示做了前列腺肿瘤切除手术的人是否将从放射治疗中获益。


再比如加州雷德伍德城(Redwood City)的Genomic Health Inc.和盐湖城(Salt Lake City)的Myriad Genetics Inc.出售能帮助辨别高、低风险前列腺癌的检测,可使病人推迟或者不采取积极治疗法。



波尔金霍恩医生说,去除雄性激素肿瘤相当于去掉前列腺癌细胞的防晒霜,使其对放疗更敏感。这份报告于去年11月份在医学期刊《癌症发现》(Cancer Discovery)上发表。



现年77岁,刚刚退休的整形外科医生霍华德·贝林(Howard Bellin)于去年10月份通过手术切除了他患有癌症的前列腺,目前正在接受新疗法。贝林医生说,传统疗法是要医生在手术后观察肿瘤是否会复发,然后再采用更积极的疗法或激素疗法。他说,他目前服用两种激素药物并接受放疗,希望“直接上猛药”可以找到治愈这一癌症的妙方。