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決策輔助工具摘要表

左側轉移性大腸直腸癌, 我該選擇哪種標靶注射藥物治療? 最新更新日期:2019年11月26日
科別 內科,外科
主題類別 10. 腫瘤
決策類型 治療
關鍵字 左側野生型轉移性大腸直腸癌、Bevacizumab (Avastin, 癌思停注射劑)、Cetuximab (Erbitux, 爾必得舒注射液)、Panitumumab (Vectibix, 維必施注射劑) 、GRADEpro (The Grading of Recommendations Assessment, Developmentand Evaluation, 證據等級)、LOE (level of evidence, 證據等級)、整體病況改善(objective response rate)、腫瘤縮小進行手術切除率(early tumor shrinkage )、疾病無惡化存活率(progression-free survival)及整體存活率(overall survival)
適用病人條件 左側轉移性大腸直腸癌患者且基因檢測無突變(即左側基因野生型轉移性大腸直腸癌)
可供選擇決策方案 Bevacizumab (Avastin, 癌思停),Cetuximab (Erbitux, 爾必得舒), Panitumumab (Vectibix, 維必施)
使用場所 診間、病房
執行者 醫師
開發團隊、機構 高雄榮民總醫院※本決策輔助工具由國民健康署部分經費補助
團隊成員
版本
輔助工具研發過程說明 一、 界定範圍:
依據2015年國民健康署癌症年報統計,大腸直腸癌發生率於男女性分別為第一名及第二名,而死亡率為第三名1。以往的數據及文獻顯示,大腸直腸癌較常發生的位置在左側大腸,左側發生率(66%)大於右側(33%),其中約25%病人初診斷即為轉移性大腸直腸癌,50%病人將由前期大腸直腸癌惡化為轉移性大腸直腸癌“。但大腸直腸癌死亡率卻非第一名的主因在於發現轉移時,接受有效的標靶治療,進而降低死亡率。若病人未接受及時適切的標靶治療,死亡率則高達八成,且存活時間不到2年,整體病況改善僅40.6%及腫瘤縮小僅有37.5%。依據國際治療指引指出,左側基因野生型轉移性大腸直腸癌可使用化學藥物併用標靶藥物如「癌思停」、「維必施」及「爾必得舒」。近年來我國健保陸續給付這些標靶藥物「癌思停」、「維必施」及「爾必得舒」為基因野生型轉移性大腸直腸癌第一線用藥,但使用「維必施」及「爾必得舒」治療惡化後需自費使用「癌思停」,而「癌思停」治療惡化後線使用「爾必得舒」健保仍有給付2。另一方面,2017年文獻指出「左側」基因野生型轉移性大腸癌「維必施」及「爾必得舒」可能比「癌思停」有療效6,但「維必施」及「爾必得舒」之副作用比「癌思停」常見。依目前健保給付規定使用「維必施」及「爾必得舒」後,若因疾病惡化改用「癌思停」需自費使用。因此,協助「左側」基因野生型轉移性大腸直腸癌之患者選擇一個有效且可以接受之副作用及費用就相當重要。

二、使用者需求調查:
今年初在大腸直腸外科科務會議中提出討論並以問卷方式分析「PDA需求評估」調查,統合科內各職類同仁之意見,發現無論是臨床意義重要性、急迫性、實用性、縮短解釋病情時間、個案數及降低醫療糾紛,「左側基因野生型轉移性大腸直腸癌,我該選擇哪種標靶藥物治療?」都是目前科內最在意的問題。(問卷調查人數及身份:共醫療人員11人,其中5位大腸直腸外科主治醫師、2位大腸直腸外科總醫師、2位大腸直腸外科專科護理師及2位藥師)

依據文獻資料提供之療效及副作用項目,以問卷方式調查病人及醫療人員考量之程度,再依此需求之選項進行決策輔助工具之製作。(問卷調查人數及身份:共14人。醫療人員11人,其中5位大腸直腸外科主治醫師、2位大腸直腸外科總醫師、2位大腸直腸外科專科護理師及2位藥師:左側轉移性大腸直腸癌病人3人)

三、證據檢索及整合
使用 metastatic colorectal cancer, cetuximab, panitumumab, bevacizumab 及其相關同義字等自然語言和MeSH term為關鍵字,於PubMed 、Cochrane library 及 EMBASE等大型資料庫,進行搜尋並評讀文獻品質,最后納入14篇品質良好的隨機分配研究,利用Review Manager 5.3 及 STATA 15 MP4統計軟體整合比較不同標靶藥物之療效及副作用,利用GRADEpro 及 OxfordLOE 2011評定證據等級。

P:left-sided metastatic colorectal cancer, RAS wild type
I :Cetuximab (anti-EGFR) , panitumumab(anti-EGFR)
C :Bevacizumab (anti-VEGF)
O :
Overall survival (OS)
Progression-free survival (PFS)
Overall response rate (ORR)
Adverse effect

重要結論:
2.1 Panitumumab:
2.1.1療效:腫瘤縮小可手術切除率最好
2.1.2副作用:嚴重副作用需住院及皮膚痤瘡狀紅疹最多
2.2 Cetuximab :
2.2.1 療效: 疾病無惡化存活率及整體存活率及整體病況改善率最好
2.2.2 副作用: 嚴重副作用須住院及皮膚痤瘡狀紅疹介於中間
2.3 Bevacizumab:
2.3.1 療效: 疾病無惡化存活率︾整體存活率︾整體病況改善率及縮小腫瘤可
手術切除率最差
2.3.2 副作用:嚴重副作用須住院及皮膚痤瘡狀紅疹最少

四、測試與修訂
完成之決策輔助工具以alphatest進行「質性」(民眾5人:醫療人員6人)之問卷調查分析,再針對民眾及醫療人員之意見修正決策輔助工具內容。接著再找另外一些民眾及醫療人員以alphatest進行「量性」(民眾8人醫療人員7人)之問卷調查分析,評估病人及醫療人員對此決策輔助工具之認知程度及實用滿意度。因大部份alpha test量性問卷顯示,此決策輔助工具認知程度及實用滿意度皆大於4分,再將此份決策輔助工具實際使用於左側基因野生型轉移性大腸直腸癌病人后,又進行beta test之分析(病人病人家屬2人醫療人員7人),期待能更貼近臨床使用之需求。
參考文獻 1. 國民健康署104 年癌症登記年報〈
https://www.hpa.gov.tw/Pages/ashx/File.ashx?FilePath=~/File/Attach/8084/File_7635.pdf
2. 中央健康保險署之藥品給付規定〈http://www.nhi.gov.tw/02hospital/hospital_file/chap9.doc
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25. https://gradepro.org/
26. Bevacizumab (Avastin, 癌思停注射劑) ︽ Cetuximab (Erbitux, 爾必得舒注射液) ︽
Panitumumab (Vectibix, 維必施注射劑) 仿單
27. 牛津大學實證醫學中心第二版 (https://www.cebm.net/?p=63)
醫病共享決策介紹
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