台灣攝護腺癌病人使用雄性素剝奪治療之效果及安全性評估

Assessing Effectiveness and Safety of Androgen Deprivation Therapy in Patients with Prostate Cancer in Taiwan

姜思羽(Szu-Yu Chiang)

指導教授 ： 黃耀斌

高雄醫學大學/藥學院/藥學系臨床藥學碩士班/碩士(2017年)

摘要

研究背景以及研究目的：
荷爾蒙治療，又稱雄性素剝奪治療，是攝護腺癌病人可以選擇的治療之一。雄性素剝奪治療可分為外科手術雙側睪丸切除，以及藥物去勢療法。根據多篇研究顯示，雄性素剝奪治療可能會增加相關糖尿病罹患風險以及心血管疾病，包括心肌梗塞以及中風。除此之外，目前台灣攝護腺癌病人之風險以及效益評估相關資料仍不足。本研究將探討攝護腺癌病人接受雄性素剝奪治療之療效與安全性。
研究方法：
本研究使用2005年百萬人承保抽樣歸人檔，進行回溯性世代研究。納入於1998到2012年新診斷攝護腺癌病人，分為接受雄性素剝奪治療與未接受雄性素剝奪治療療兩組。主要研究事件為全死因死亡事件，次要研究事件為中風以及急性心肌梗塞。研究觀察時間到2013年12月。利用Cox迴歸分析(cox regression)評估不同治療模式其風險比(Hazard Ratios)與95%信賴區間。
研究結果：
本研究納入1,057位符合我們研究設計之攝護腺癌病人。經由傾向分數一比一配對後，其中389位病人為接受雄性素剝奪治療組，389位病人為未接受雄性素剝奪治療組別。關於中風事件之風險，雄性素剝奪治療使用組與未使用組別相比，並沒有達到統計學上顯著差異(adjusted HR=1.267, 95% CI=0.774-2.076)。在急性心肌梗塞事件風險中，也沒有達到統計學上顯著差異(adjusted HR=1.005, 95% CI=0.570-1.772)。但在全死因死亡風險方面，卻發現使用雄性素剝奪治療組別顯著增加死亡風險(adjusted HR=2.461, 95%CI=1.834-3.303)。

研究結論：
本研究結果顯示，雄性素剝奪治療對於攝護腺癌病人而言，顯著增加全死因死亡風險。但是在中風以及心肌梗塞發生風險方面，並沒有顯著增加其風險。未來仍需進一步使用其他大型資料庫探討此議題。

關鍵字

攝護腺癌 ； 荷爾蒙治療 ； 雄性素剝奪治療 ； 全死因死亡 ； 中風 ； 急性心肌梗塞

並列摘要

Background and objective:
Hormone therapy, known as androgen deprivation therapy (ADT), is one of the treatment options for prostate cancer patients. ADT includes surgical bilateral orchiectomy and medical therapy. In several studies, ADT was found to increase the risk of diabetes and cardiovascular disease, including myocardial infarction and stroke. Furthermore, there are few studies evaluating the effectiveness and safety of ADT in Taiwanese population.
Our study aimed to evaluate the effectiveness and safety of medical androgen deprivation therapy in patients with prostate cancer in Taiwan.
Methods:
We conducted a population-based retrospective cohort study from Longitudinal Health Insurance Database 2005 (LHID2005) for the analysis. We enrolled newly diagnosed prostate cancer patients from 1998 to 2012, and divided patients into ADT users and non-user group. Primary outcome was all-cause mortality. Secondary outcomes were stroke, and acute myocardial infarction (AMI). Follow-up was complete through December 2013. Hazard ratio, with 95% confidence intervals, were estimated with the use of a Cox proportional-hazards model.
Results:
In total 1,057 prostate cancer patients who met our study criteria were enrolled in our study. After 1 to 1 propensity score matching, there were 389 patients in ADT user group and non-user group, respectively. No significant increased risk of stroke (adjusted HR=1.267, 95% CI=0.774-2.076), and AMI (adjusted HR=1.005, 95% CI=0.570-1.772) were found between user and non-user group. In contrast, we found an increasing risk of all-cause mortality (adjusted HR=2.461, 95%CI=1.834-3.303) in ADT-user group.
Conclusion:
In conclusion, medical ADT for patients with prostate cancer was at a higher risk of all-cause mortality with a statistical difference compared to non-user group. No significantly increased risk of stroke and acute myocardial infarction were found in patients receiving ADT. Further research is needed to confirm our findings from National Health Insurance Administration database of larger population.

並列關鍵字

Prostate cancer ； hormone therapy ； androgen deprivation therapy (ADT) ； all-cause mortality ； stroke ； acute myocardial infarction

參考文獻

1. Health Promotion Administration MoHaWT. [July 18, 2017]. Available from: https://cris.hpa.gov.tw/pagepub/Home.aspx.

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