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附錄
附錄一 Inlyta (axitinib)樞紐試驗 Study A4061032 [47]
根據歐洲藥品管理局(European Medicines Agency, EMA)所公布的評估報告，2012 年 5 月，axitinib 獲得歐盟國家的上市許可，適應症內容為“for the treatment of adult patients with advanced renal cell carcinoma (RCC) after failure of prior treatment with sunitinib or a cytokine.“，核准的用法用量為，起始治療劑量是一 天兩次每次 5mg，醫師可依照個別病人對藥物的反應進行劑量調整。如果病人可 以良好的耐受起始劑量，並且沒有血壓升高、服用降血壓藥物等情形，醫師可以 將治療劑量首先調升至一天兩次每次 7mg，最高的治療劑量為一天兩次每次 10mg。
我國核准之 axitinib 適應症內容與歐洲藥品管理局所核准之適應症內容相同。美 國食品藥品管理局(US FDA)於 2012 年 1 月核准 axitinib 上市，核准的適應症內 容為「Inlyta is a kinase inhibitor indicated for the treatment of advanced renal cell carcinoma after failure of one prior systemic therapy.」，核准的用法用量與歐洲藥品 管理局所核准者相同[48]。
1. 試驗目的：
執行此項試驗主要用以證明，與 sorafenib 相比，axitinib 在治療接受過一次 全 身 性 系 統 治 療 ( 例 如 sunitib 、 bevacizumab+IFN- α 、 temsirolimus 、 cytokine(s)、或這些藥物的組合療法)失敗後的晚期腎細胞癌(advanced RCC) 病人的療效和安全性方面表現。
2. 試驗設計：
此項試驗是一項為期三年、公開標籤、隨機分派、多中心(22 個國家 175 個 臨床試驗中心)、活性對照(active-controlled)的第三期臨床研究。
3. 受試者納入/排除標準：
主要納入標準：
(1) 年齡大於等於 18 歲 (2) 男性或女性皆可
(3) 經組織學或細胞學檢驗確診為腎細胞癌之病人，且其病理分類需為亮細 胞型(clear cell type)，並有腫瘤轉移之證據。
(4) 病人需有至少一處可測量的目標病灶(具 CT 或 MRI 報告)。
(5) 進入試驗前曾經歷過一次系統性的第一線治療(治療晚期腎細胞癌)。
(6) 先 前 的 治 療 方 案 需 包 括 下 列 藥 物 的 其 中 一 種 或 多 種 ： sunitinib 、 bevacizumab+IFN-α、temsirolimus 或 cytokine(s)。
(7) 先前進行的系統性治療、放射治療或手術治療，需在進入本試驗前至少 兩周結束該項治療(如為接受 bevacizumab+IFN-α治療者，需在進入試驗 前 4 周結束治療)。
(8) 病人的身體情況良好，ECOGa分數為 0 或 1，壽命預估(life expectancy) 大於等於 12 周以上。
主要排除標準：
(1) 先前接受過超過一項以上的系統性治療。
(2) 先前接受過輔助性(adjuvant)或新輔助性(neoadjuvant)的系統性治療。
(3) 在進入試驗前四周內接受過手術治療，或者在進入試驗前兩周內接受過 放射治療。
(4) 針對轉移病灶的支持性放射線治療(palliative radiotherapy)，已獲得許可 得以進行，並且至少有一個病灶並未接受過放射線治療。
4. 試驗藥物與治療方式：
依據受試者其身體情況(ECOG 分數)與其先前接受過的治療方案為何，以 1:1 的比例隨機分派到下列各組之中。治療是以四周為一個療程。在試驗過程 中，化學治療或者其他實驗性抗癌治療(experimental anticancer treatments)都 不可以同時進行。對於疾病相關症狀的支持性治療可以同時進行。支持性的 放射線治療僅被准許給予在疼痛控制或骨骼疾病出現時。
試驗組：
受試者被給予一天兩次每次 5mg 的 axitinib。Axitinib 需與食物同時服用。
如果受試者可以良好的耐受 axitinib 的起始劑量，連續兩周都沒有發生 CTCAEb二級以上的副作用，則建議將劑量調整至一天兩次每次 7mg axitinib，隨後，除非受試者的血壓高於 150/90mmHg，或者受試者服用降血 壓藥，最高可以將劑量調整至一天兩次每次 10mg axitinib。另一方面，如果
a ECOG 數值是一種評估癌症患者日常體能狀態的方法，可以用來做為病患是否適合接受治療的
評斷標準之一。 ECOG 數值由 0 到 4 分，數值越高者，代表病患體能狀態越差，帄均存活時 間越短。
b不良事件常用術語標準(Common Terminology Criteria for Adverse Events, CTCAE)被廣泛用於癌
b不良事件常用術語標準(Common Terminology Criteria for Adverse Events, CTCAE)被廣泛用於癌