Androgen Deprivation Therapy for Prostate Cancer: What to Know
It may seem违反直觉的,但医生有时疼痛。病人就医时最多问主诉ts to periodically skip doses of critical medications on purpose. Among other benefits, these so-called “drug holidays” can offer a break from a drug’s side effects. And for some diseases like prostate cancer, an on-off treatment cycle may be used to boost a patient’s response to a drug whose effectiveness has begun to wane.
该策略有时用于给出正在进行的激素治疗的前列腺癌患者在治疗方案中延长突破。被称为间歇性雄激素剥夺（或间歇性雄激素抑制），这种治疗方法提供了更好的生活质量的前景，虽然它不是治愈性的，但延长生存的希望。
因此，间歇性雄激素剥夺因近30年前第一次描述而越来越受欢迎。然而，尽管使用不断增长，但仍有重要问题。可以从治疗中休息真正延长一个男人的生命，或者可能会缩短他的生命？
The limits of androgen deprivation
To better appreciate the rationale for intermittent therapy, it helps to understand the role of androgens in prostate cancer development and the shortcomings of continuous androgen deprivation.
The growth of prostate tumors is stimulated by androgens, or male hormones. The two most common androgens are testosterone and dihydrotestosterone (DHT). Since the Nobel Prize-winning discovery that prostate tumors depend on these hormones to grow, reducing androgen levels or blocking the action of androgen has become the standard of care for men with cancer that has spread beyond the prostate to the bones and other organs.
在使用它的男人中也一直越来越兴趣特异性抗原（PSA）水平在用手术或辐射治疗后开始上升（生化复发）。生物化学复发是一种早期迹象，即癌症尚未消除。
Today, androgen deprivation is usually achieved with drugs that block the signals for androgen production by the testicles (luteinizing hormone-releasing hormone agonists, LHRHa) or block their action (receptor blockers and antiandrogens), or drugs that directly block the synthesis of androgens. Therapy is typically administered on a daily basis, and initially it is very effective.
然而，遗憾的是，随着前列腺癌细胞能够在不接触男性激素的情况下，它的效果淡化了几个月或多年。
此外，雄激素剥夺治疗的男性可能会对他们的身心健康和生活质量产生各种不利影响，包括热闪光，勃起功能障碍，骨质疏松症，肌肉损失，体重增加和抑郁症。
Why intermittent therapy?
Interrupting treatment causes a man’s testosterone level to rise, re-exposing the prostate tumor to androgens. Some research has suggested that this may trigger cellular changes that make the cancer vulnerable to hormone therapy for a longer time.
虽然间歇性雄激素剥夺方案变化，但典型的循环可能是六至九个月的药物，然后是平等的脱离治疗。然而，患者将在休息期间密切监测治疗，以及他的癌症恶化的任何迹象（如上升的PSA水平）将表明需要恢复治疗。
To learn more about on-and-off hormonal treatment, doctors in Canada launched an international study comparing 690 men who underwent intermittent androgen deprivation with another 696 men who received standard continuous hormone treatment.
The men selected to participate had undergone放射治疗for cancer that was localized—that is, confined to the prostate—but had experienced a biochemical recurrence. (Some of the men initially had手术to remove their prostates, but required follow-up radiation therapy.)
None of the men reported having prostate cancer symptoms. For the study, most of the participants received injections of an LHRHa, plus an antiandrogen drug. Men in the intermittent group received therapy for eight months at a time before taking breaks.
这项研究的结果发表在2012年n新英格兰医学杂志. On the pressing question of survival time, the investigators found the two groups to be similar: The typical man receiving intermittent therapy lived 8.8 years, compared with 9.1 years in the continuous-therapy group, a small difference that may have occurred by chance.
A little more than a half year after publication of the Canadian study’s findings,新英格兰医学杂志published the results of another large trial comparing intermittent androgen deprivation and continuous therapy in prostate cancer patients. This study was overseen by doctors in the United States, but like the Canadian-led study it also involved a large number of men from clinics in several countries.
Included were 770 men who received intermittent therapy and 765 men who had continuous hormone treatment. However, in contrast to the Canadian investigation, the men in this study had more advanced cancer that had begun to metastasize, or spread, to the bones and other organs.
In the U.S.-led study, men who received continuous therapy lived longer than their counterparts in the intermittent therapy group: 5.8 years, compared to 5.1 years, a modest but significant difference. Further, the authors estimated that men in the intermittent therapy group were about 10 percent more likely to die than the continuously treated men, though they argue that the actual risk might really be twice that.
本研究的作者推测，如果加拿大审判持续更长时间，也可能发现连续治疗组中的男性更长时间。另一方面，2013年审查九项试验审查发现，接受局部，晚期或转移前列腺癌的细胞间或连续雄激素剥夺的男性之间的存活率没有总体差异。
Interestingly, data from this review show that while men who opt for intermittent therapy are more likely to die of prostate cancer, those numbers are offset by equally high rates of deaths from other causes in men who have continuous hormone treatment.
A better life?
a也许较少有关间歇性治疗的烦恼问题：它是否提高了一个人的生活质量？为了澄清，加拿大和美国都是新英格兰杂志研究审查了这个问题。
In the Canadian study, which looked at men with prostate-confined cancer, those who received intermittent therapy reported significantly fewer problems associated with hormone treatments, such as hot flashes, erectile dysfunction, low libido (or desire for sexual activity), and fatigue.
在对患有转移性前列腺癌的男性的研究中，那些接受间歇治疗的人首先报道了更好的勃起功能和心理健康，但两组之间几乎没有差异。
Many other studies also show that patients have fewer side effects and enjoy better quality of life during the off-treatment phase of intermittent androgen deprivation. Some research suggests that men may derive certain long-term benefits from scheduled breaks in hormone treatments.
For instance, a few studies offer clues that intermittent therapy might reduce a man’s risk for developing conditions such as heart disease and osteoporosis. However, data to support those claims are limited.
The bottom line
毫无疑问，对间歇性雄激素剥夺的益处会进一步辩论。未来的研究可能会检查涉及不同时间和不同药物的策略新英格兰杂志studies.
For now, however, it’s probably safe to say that this treatment strategy doesn’t prolong survival. For most men with advanced metastatic prostate cancer, continuous therapy is likely to remain the standard of care.
It’s worth noting that there is no consensus regarding the use of androgen deprivation—continuous or intermittent—in men who have had a biochemical recurrence following surgery or radiation.
研究表明，在这种情况下，某些男性对未经转移的十年或更长时间来说，某些男性并不罕见。因此，对于处于发育转移性疾病的低风险的男性（治疗后的PSA倍增时间和诊断后的诊断后的PSA倍增），转移迹象前的荷尔蒙治疗风险可能超过了这种益处。
但对于在发育转移性疾病的高风险（治疗后Psadt少于9个月的PsAdt和诊断时的PSA），雄激素剥夺 - 甚至间歇性抑制 - 可能是合理的选择;后者似乎最小化了激素治疗的副作用而不会影响人类生存的机会。
Learn more aboutThe Best Treatment for Every Prostate Cancer Risk Group和Prostate Cancer Clinical Trials.
