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Maximal androgen blockade for advanced prostate cancer

  • Review
  • Intervention

Authors


Abstract

Background

Prostate cancer is the second leading cause of cancer death in men. Long standing observations have found prostate cancer responsive to androgen suppression. The primary approach to androgen suppression for men with advanced disease (cancer that has spread outside the prostate gland) has been castration. However, medical or surgical castration eliminates only 90% to 95% of the daily testosterone production. The remainder is produced in the adrenal glands. In the 1980s Labrie hypothesized that counteracting adrenal androgens would further inhibit tumor growth and possibly improve symptoms and survival beyond the response achieved with monotherapy. In response to this hypothesis a number of anti-androgen agents were identified and used in combination with medical or surgical castration to obtain maximal androgen blockade (MAB). Despite multiple clinical trials and several meta-analyses the clinical efficacy and cost effectiveness of MAB compared with monotherapy has not been clearly established.

Objectives

This systematic review assessed the effect of maximal androgen blockade (MAB) on survival when compared to castration (medical or surgical) alone for patients with advanced prostate cancer.

Search methods

Randomized controlled trials were searched in general and specialized databases (MEDLINE, EMBASE, Cancerlit, Cochrane Library, VA Cochrane Prostate Disease register) and by reviewing bibliographies.

Selection criteria

All published randomized trials were eligible for inclusion provided they (1) randomized men with advanced prostate cancer to receive a non-steroidal anti-androgen (NSAA) medication in addition to castration (medical or surgical) or to castration alone, and (2) reported overall survival, progression-free survival, cancer-specific survival, and/or adverse events. Eligibility was assessed by two independent reviewers.

Data collection and analysis

Information on patients, interventions, and outcomes were extracted by two independent reviewers using a standardized form. The main outcome measure for comparing effectiveness was overall survival at one, two, and five years. Secondary outcome measures included progression-free survival and cancer-specific survival. The relationship of specific NSAA on outcome was evaluated. Additionally, the incidence of adverse effects was measured.

Main results

Twenty trials enrolling 6320 patients were included. The pooled OR for overall survival was 1.03 (95% CI:0.85 to 1.25), 1.16 (95% CI:1.00 to 1.33), and 1.29 (95% CI:1.11 to 1.50) at 1, 2, and 5 years respectively. Overall survival was only significant at five years. The risk difference at 5 years was 0.048 (95% CI:0.02 to 0.077) and NNT at 5 years 20.8. Progression-free survival was improved only at 1-year follow up (OR = 1.38) and cancer-free survival was improved only at 5 years (OR = 1.22). Adverse events occurred more frequently in those assigned to MAB and resulted in withdrawal in 10%. Quality of life was measured in only one study favored orchiectomy alone (less diarrhea and better emotional functioning in the first six months).

Authors' conclusions

MAB produces a modest overall and cancer-specific survival at five years but is associated with increased adverse events and reduced quality of life.

摘要

背景

以最大男性荷爾蒙阻斷治療侵犯性前列腺癌

前列腺癌為男性癌症死因之第二位。長期觀察研究顯示抑制男性荷爾蒙可用於治療前列腺癌。去勢為抑制男性荷爾蒙之原始療法,用以治療男性侵犯性前列腺癌(指癌細胞已侵犯至前列腺本體之外)。然而,藥物或手術去勢僅能消除90−95%每日製造的睪固酮,其餘男性荷爾蒙由腎上腺製造。1980年代,Labrie假設抑制由腎上腺分泌之男性荷爾蒙可進一步抑制腫瘤生長,並可能使病人之症狀和生存年限都較單一治療更進步。因應此假說,發展出數種抗男性荷爾蒙藥物與手術或藥物去勢並用以達到最大男性荷爾蒙阻斷(MAB)。雖然過去有許多的臨床試驗和研究分析,但是與單一治療相比,最大男性荷爾蒙阻斷的臨床效果和成本效益仍未清楚建立。

目標

此系統性回顧評估對於患有侵犯性前列腺癌之病人,最大男性荷爾蒙阻斷與單一去勢療法(藥物或手術)相比,其存活情況。

搜尋策略

在一般及專業的資料庫(MEDLINE, EMABASE, Cancerlit, Cochrane Library, VA Cochrane Prostate Disease register)中搜尋臨床隨機對照試驗,並檢閱書目資料。

選擇標準

所有已公開發表的隨機臨床試驗需符合下列兩要點:(1)、隨機選取患有侵犯性前列腺癌的男性,且這些病人除去勢(以藥物或手術方式)之外,都接受非類固醇之抗荷爾蒙藥物;(2)、需報告總存活率、無惡化存活率、癌症專一存活率和所有副作用。由兩名審查者審閱這些著作。

資料收集與分析

兩名審查者以標準化格式審查病人、病人所接受的治療和治療結果。主要評估治療效果的項目為一年、二年與五年總存活率。次要項目為無惡化存活率與癌症專一存活率。特定非類固醇類抗荷爾蒙藥物的療效亦列入評估。除此之外,也記錄副作用之發生率。

主要結論

20個臨床試驗,包括了6,320位病人納入本次的評估。1年、2年與5年總存活率的勝算比分別為1.03 (95% CI 0.85−1.25)、1.16 (95% CI 1.00−1.33)與1.29 (95% CI 1.11−1.50)。總存活率僅在第5年時才有顯著差異。第5年時的risk difference為0.048 (95% CI 0.02−0.077),NNT為20.8。無惡化存活率僅在第1年追蹤時有改善(勝算比 = 1.38),而癌症專一存活率也僅在第5年時有改善(勝算比 = 1.22)。副作用較常發生在使用最大男性荷爾蒙阻斷組病患,有10%病人會因此而停止此治療。僅有1個試驗有評估生活品質,此試驗認為單純接受睪丸切除的病人生活品質較佳(前6個月較少腹瀉且情緒較佳)。

作者結論

最大抗男性荷爾蒙阻斷治療,對於5年總存活率和癌症專一存活率,雖然有一些效果存在,但也會增加副作用並降低生活品質。

翻譯人

本摘要由臺灣大學附設醫院姜宜妮翻譯。

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

最大抗男性荷爾蒙阻斷治療有機會使患有侵犯性前列腺癌的病患得到較高的存活率,但並非所有男性都適用。前列腺腺體在老年男性身上常有癌化現象。前列腺癌的治療包括手術及放射線治療。男性荷爾蒙會刺激前列腺癌生長。荷爾蒙抑制療法能降低男性荷爾蒙並藉此試圖治療此癌症。最大男性荷爾蒙阻斷治療就是使用藥物以達到完全阻斷男性荷爾蒙。此回顧發現,最大男性荷爾蒙阻斷治療對於延長患有侵犯性前列腺癌男性之存活率雖然有一些效果存在,然而此種療法也有其副作用而無法適用於所有病患。

Plain language summary

Maximal androgen (hormone) blockade therapy may improve chances of longer survival in men with advanced prostate cancer, but may not be suitable for all men.

The prostate gland is a common site of cancer in older men. Treatments for prostate cancer include surgery and radiation therapy. Male hormones (androgens) stimulate prostate cancer growth. Hormone suppression therapy, which decreases hormone levels, is therefore also used to try to treat the cancer. Maximal androgen blockade (MAB) uses drugs to completely block male hormones. The review found that there is modest evidence that MAB improves the chances of longer survival for men with advanced prostate cancer. However, there are also adverse effects of MAB treatment that may mean that it is not a suitable treatment for all men.

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