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34. Sabel M, Giese A. Safety profile of carmustine wafers in malignant glioma: a review of controlled trials and a decade of clinical experience. Current Medical Research and Opinion 2008; 24(11): 3239-3257.
35. Westphal M, Ram Z, Riddle V, Hilt D, Bortey E. Gliadel® wafer in initial surgery for malignant glioma: long-term follow-up of a multicenter controlled trial. Acta Neurochir (Wien) 2006; 148(3): 269-275.
36. Subach BR, Witham TF, Kondziolka D, Lunsford LD, Bozik M, Schiff D.
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37. Chaichana KL, Zaidi H, Pendleton C, et al. 1730 The Efficacy of Carmustine Wafers for Older Patients with Glioblastoma Multiforme: Prolonging Survival In: 2010 CNS Annual Meeting; October 16-21, 2010; San Francisco,
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38. Bota D, Desjardins A, Quinn J, Affronti M, Friedman H. Interstitial
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40. Gutenberg A, Lumenta CB, Braunsdorf WEK, et al. The combination of carmustine wafers and temozolomide for the treatment of malignant gliomas.
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41. McGirt MJ, Than KD, Weingart JD, et al. Gliadel (BCNU) wafer plus concomitant temozolomide therapy after primary resection of glioblastoma multiforme. Journal of Neurosurgery 2009; 110(3): 583-588.
42. Duntze J, Litré C-F, Eap C, et al. Implanted Carmustine Wafers Followed by Concomitant Radiochemotherapy to Treat Newly Diagnosed Malignant Gliomas: Prospective, Observational, Multicenter Study on 92 Cases. Ann Surg Oncol 2013; 20(6): 2065-2072.
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44. PUBLIC SUMMARY DOCUMENT: CARMUSTINE, implant, 7.7 mg, Gliadel® for he treatment of newly-diagnosed high-grade malignant glioma
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45. PUBLIC SUMMARY DOCUMENT: Carmustine, implant, 7.7 mg, Gliadel® for expanding the patient population of the current Pharmaceutical Benefits Scheme (PBS) restriction for carmustine to include high grade malignant gliomas rather than limiting treatment to patients with glioblastoma multiforme. Pharmaceutical Benefits Advisory Committee.
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Accessed June 20, 2014.
46. PUBLIC SUMMARY DOCUMENT: Carmustine, implant, 7.7 mg, Gliadel® for expanding the current restricted benefit listing to include the treatment of recurrent glioblastoma multiforme in patients for whom surgical resection is indicated. Pharmaceutical Benefits Advisory Committee.
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47. PUBLIC SUMMARY DOCUMENT: Carmustine, implant, 7.7 mg, Gliadel® for expanding the current restricted benefit listing to include the treatment of recurrent glioblastoma multiforme (GBM) in patients for whom surgical resection is indicated and recurrence has occurred within 6 months of
temozolomide or where temozolomide is contraindicated or not tolerated due to side effects. Pharmaceutical Benefits Advisory Committee.
http://www.health.gov.au/internet/main/publishing.nsf/Content/0FE90DDCB5 E3B618CA257BF00018CBD6/$File/Carmustine%20Final%20%20PSD%20 Orphan.pdf. Published 2008. Accessed June 20, 2014.
48. Yung WK, Albright RE, Olson J, et al. A phase II study of temozolomide vs.
procarbazine in patients with glioblastoma multiforme at first relapse. Br J Cancer 2000; 83(5): 588-593.
49. Brem H, Piantadosi S, Burger PC, et al. Placebo-controlled trial of safety and efficacy of intraoperative controlled delivery by biodegradable polymers of chemotherapy for recurrent gliomas. The Polymer-brain Tumor Treatment Group. Lancet 1995; 345(8956): 1008-1012.
50. National Institute for Health And Clinical Excellence (NICE). TA 121
Carmustine implants and temozolomide for the treatment of newly diagnosed
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附錄
附錄一 神經膠質瘤相關藥品治療之健保給付規定[12]
第 9 節 抗癌瘤藥物 Antineoplastics drugs
9.25.Temozolomide (如 Temodal)：(94/3/1、97/1/1、98/9/1) 附表八之二 限用於
1.經手術或放射線治療後復發之下列病人：
(1)退行性星狀細胞瘤(AA- anaplastic astrocytoma)
(2)多形神經膠母細胞瘤(GBM -Glioblastoma multiforme)
(3)退行性寡樹突膠質細胞瘤(anaplastic oligodendroglioma) (98/9/1)
2.新診斷的多形神經膠母細胞瘤，與放射線治療同步進行，然後作為輔助性 治療。（97/1/1）
3.需經事前審查核准後使用。
4.若用於退行性寡樹突膠質細胞瘤，每日最大劑量 200mg/m2。每次申請事 前審查之療程以三個月為限，再次申請時需附上治療後相關臨床評估資 料並檢附 MRI 或 CT 檢查，若復發之惡性膠質細胞瘤有惡化之證據，則 必須停止使用。(98/9/1)
9.35.carmustine 植入劑 (如 Gliadel Wafer)：(100/2/1)附表八之四 1.作為復發性多形神經膠母細胞瘤病人的手術輔助，且不得與
temozolomide 併用。
2.需經事前審查核准後使用。
9.37.Bevacizumab (如 Avastin)：（100/6/1）(101/05/1)附表九之十 1.轉移性大腸或直腸癌：
(1)Bevacizumab 與含有 irinotecan/ 5-fluorouracil/ leucovorin 或
5-fluorouracil/ leucovorin 的化學療法合併使用，作為轉移性大腸或直腸 癌患者的第一線治療。
(2)使用總療程以 24 週為上限。
2.惡性神經膠質瘤(WHO 第 4 級) - 神經膠母細胞瘤：
單獨使用可用於治療曾接受標準放射線治療且含 temozolomide 在內之 化學藥物治療失敗之多型性神經膠母細胞瘤(Glioblastoma multiforme)復 發之成人患者。(101/05/1)
3.本藥須經事前審查核准後使用，每次申請事前審查之療程以 12 週為限，
再次申請必須提出客觀證據（如：影像學）證實無惡化，才可繼續使用。
附錄二 本案可能的參考品之一：temozolomide 仿單建議劑量 1. 新診斷的多形神經膠母細胞瘤的成年病人
1.1 同步治療期
每療程 42 天，每天 75 mg/ m2 BSA，與放射治療（60 Gy，分成 30 次投予）同步 進行，接著給予六個療程的輔助治療。
符合全數條件者，同步治療期可延長到 49 天：絕對嗜中性白血球計數大於等於 每公升十五億個（1.5 109/L），血小板計數大於等於每公升一千億個
（100 109/L），以及通用毒性標準（CTC）的非血液學毒性小於等於第一級（除 了禿髮、噁心、嘔吐以外）。
治療期間每週須測量一次全血球計數。同步治療期間應根據表一的血液學和非血 液學毒性標準，中斷或停止投予 TEMODAL。
1.2 輔助治療期
同步治療期之後四週，再給予六個療程的輔助性治療。
第一個（輔助性）療程的劑量是 TEMODAL 口服 150 mg/m2 BSA，每天一次，
投予五天，接著二十三天不用服藥。
開始第二個療程時，如果第一個療程的 CTC 非血液學毒性小於等於第二級（除 了禿髮、噁心、嘔吐以外），絕對嗜中性白血球計數（ANC）大於等於每公升十 五億個（1.5 109/L），血小板計數大於等於每公升一千億個（100 109/L），便可 將治療劑量增加為每天 200 mg/m2 BSA。
如果劑量在第二個療程沒有增加，以後的療程就不應該增加劑量。
以後每個療程最初五天的劑量要保持在每天 200 mg/m2 BSA，除非毒性出現。
輔助性治療期間，應該根據表二和表三來降低劑量。
在治療期間，第二十二天（投予第一次 TEMODAL 劑量的二十一天後）要測量 全血球計數。應該根據表三來降低 TEMODAL 的劑量或停藥。
2. 患有復發性或進行性神經膠質瘤的成人
先前未曾接受過化學治療的病人：每二十八天為一個療程，投予五天，每天一次，
口服 TEMODAL 200 mg/m2 BSA。
先前接受過化學治療的病人：在第一個療程投予初始劑量 TEMODAL 每天 150 mg/m2 BSA，在第二個療程的第一天，如果絕對嗜中性白血球計數大於等於每公 升十五億個（1.5 109/L），而且血小板計數大於等於每公升一千億個
（100 109/L），便可將治療劑量增加為每天 200 mg/m2 BSA。
TEMODAL 的劑量調整應依據取決於最低絕對嗜中性白血球計數和血小板計數 之毒性。
附錄三 相對療效之搜尋策略
1. PubMed 文獻資料庫搜尋策略與結果（搜尋日期：2014 年 7 月 22 日）
Search Query Items found
#10 #5 AND #10 AND inprocess[sb] 2
#9 #1 AND #6 AND (Randomized Controlled Trial[ptyp] AND
("2010/01/01"[PDAT] : "3000/12/31"[PDAT])) 1
#8 #1 AND #6 AND (Meta-Analysis[ptyp] OR systematic[sb]) 16
#7 1 AND #6 847
#6 #2 OR #3 OR #4 OR #5 47960
#5 "high-grade malignant glioma" 41
#4 "Glioma"[Majr] 46296
#3 "glioblastoma multiforme" 6885
#2 "Glioblastoma"[Majr] 11230
#1 carmustine 4163
2. Cochrane Library 文獻資料庫搜尋策略與結果（搜尋日期：2014 年 7 月 22 日）
No. Query Results
No. Query Results