前言鼻咽癌, 乃中國人特有之癌症根據統計 106 年 12 月底國民健康署公布的癌症年報, 國人在民國 104 年, 鼻咽惡性腫瘤發生個案數, 初次診斷為鼻咽惡性腫瘤者共計 1,492 人, 占全部惡性腫瘤發生個案數的 1.42%, 當年死因為鼻咽惡性腫瘤者共計 747 人, 死亡人數占全部惡性

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1 鼻咽癌診療指引頭頸癌多專科團隊擬定初訂修訂修訂修訂修訂修訂修訂修訂修訂

2 前言鼻咽癌, 乃中國人特有之癌症根據統計 106 年 12 月底國民健康署公布的癌症年報, 國人在民國 104 年, 鼻咽惡性腫瘤發生個案數, 初次診斷為鼻咽惡性腫瘤者共計 1,492 人, 占全部惡性腫瘤發生個案數的 1.42%, 當年死因為鼻咽惡性腫瘤者共計 747 人, 死亡人數占全部惡性腫瘤死亡人數的 1.60% 發生率的排名於男性為第 13 位女性為第 20 位民國 104 年鼻咽癌死亡率的排名於男性為第 11 位女性為第 18 位鼻咽癌發生之原因乃多重因素所構成, 經研究結果約有三項, 即遺傳因子 EB 病毒感染環境因素鼻咽癌之治療主賴放射治療, 早期 ( 第一期 ) 單用放射治療之結果就很好, 但晚期 ( 第二三四期 ) 或復發之病人可能需要併用化學及手術治療經正規治療之結果, 全部病人五年之存活率約有 60%, 早期病人可高達 90% 以上, 而晚期病人也有 50% 以上除了少數病人在治療開始就有遠端轉移其病情較難控制之外, 鼻咽癌並不是絕症, 是一種可以控制及治癒的癌症經正規方式治療以後, 病人多數能夠恢復, 而回去工作治療後, 少數病人可能復發, 所以定期追蹤檢查是必要的本院自民國 99 年藉由多專科醫師參與團隊會議共同討論的機制, 參酌 NCCN (National Comprehensive Cancer Network) 診療指引及國內外相關文獻, 進行指引改版, 以期更貼近國內民情及國際鼻咽癌診療潮流 2

3 指引修訂紀錄版本生效日期文件制定記錄新訂定 CLINICAL STAGING:T1, N1-3;T2-T4, any N, TREATMENT OF PRIMARY AND NECK: 原為 Induction chemotherapy followed by chemo/rt 修改成 Induction chemotherapy followed by RT or chemo/rt CLINICAL STAGING:Any T,any N, M1,TREATMENT OF PRIMARY AND NECK: 新增另一治療途徑為 Concurrent chemo/rt 治療前評估檢查項目 MRI with gadolinium of nasopharynx and base of skull to clavicles and CT (as indicated) with contrast 修改成 CT with contrast and/or MRI with contrast of primary and neck; Consider PET-CT for stage III-IV disease 修改成 PET-CT (option) CLINICAL STAGING:T1, N1-3; T2-T4, any N,TREATMENT OF PRIMARY AND NECK: 新增另一治療途徑為 Concurrent chemo/rt not followed by adjuvant chemotherapy 檢視本院第 5 版鼻咽癌英文版治療指引 Work up 項目 Naso pharyngeal fiberoptic examination and biopsy 刪除 and biopsy 2. 新增 Work up 項目 Biopsy of primary site or FNA of the neck 3. 新增 Work up 項目 EBV/DNA testing 4. 新增 Work up 項目 opthalmologic and endocrine evaluation as clinically indicated 檢視本院第 7 版鼻咽癌英文版治療指引新增 FOLLOW-UP RECOMMENDATIONS POST CHEMORADIATION OR RT NECK EVALUATION PATHWAY 3

4 目錄一鼻咽癌診療指引流程圖二診斷共識三治療共識四追蹤共識五鼻咽癌院內通用抗癌藥物處方六鼻咽癌放射線治療政策與程序指引七參考資料

5 一鼻咽癌診療指引流程圖 Cancer of the Nasopharynx 初版日期 :99.01 最後更新日 : WORK-UP CLINICAL STAGING TREATMENT OF PRIMARY AND NECK * H&P including a complete head and neck exam; mirror examination as clinically indicated * Nasopharyngea fiberoptic examination * Biopsy of primary site or FNA of the neck * Chest imaging * CT with contrast and/or MRI with contrast of primary and neck * PET-CT (option) * Dental evaluation as indicated * Nutrition, speech & swallowing evaluation * Bone Scan *Abdominal echo * EBV/DNA testing * Ophthalmologic and endocrine evaluation as clinically indicated * Multidisciplinary consultation T1, N0, M0 T1, N1-3; T2-T4, any N Any T, any N, M1 Definitive RT to nasopharynx And elective RT to neck CCRT followed by adjuvant chemotherapy CCRT not followed by adjuvant chemotherapy Induction chemotherapy followed by R/T or chemo/rt Platinum-based combination chemotherapy Concurrent Chemo/RT See Follow-Up Recommendations Post Chemoradiation or RT See Follow-Up Recommendations Post Chemoradiation or RT RT to primary and neck or Chemo/RT See Follow-Up Recommendations Post Chemoradiation or RT p2 p2 p2 1.physical exam : Year 1, every 1 3 month Year 2, every 2 4 month Years 3 5, every 4 6 month >5 years, every 6 12 month 2.Further reimaging as indicated based on signs/symptoms 3.Chest imaging as clinically indicated 4.Thyroidstimulating hormone (TSH) every 6-12 mo if neck irradiated 5.Speech/hearing and swallowing evaluation and rehabilitation as clinically indicated 6.Smoking cessation and alcohol counseling as clinically indicated P1 5

6 Cancer of the Nasopharynx 初版日期 :99.01 最後更新日 : FOLLOW-UP RECOMMENDATIONS POST CHEMORADIATION OR RT NECK EVALUATION After systemic therapy/rt Or RT 4 8 weeks clinical assessment as appropriate Residual primary, persistent disease or progression If response To assess extent of disease or distant metastases: CT ofprimary and neck and/or MRI with contrast (4 8 wk) PET/CT PET/CT at Minimum 12 wk CT of primary and neck and/or MRI with contrast at 8 12 wk If diagnosis confirmed or progression If imaging is positive, CT of primary and neck or MRI with contrast Imaging positive Imaging negative Resection of residual primary and/or neck dissection Assessment of disease status Then choice of surgery or RT or systemic therapy or observation PET imaging at 12 wk Neck dissection Observation 1. physical exam : Year 1, every 1 3 mo Year 2, every 2 4 mo Years 3 5, every 4 6 mo > 5 years, every 6 12 mo 2.Further reimaging as indicated based on signs/symptoms 3.Chest imaging as clinically indicated 4.Thyroid-stimulating hormone (TSH) every 6-12 mo if neck irradiated 5.Speech/hearing and swallowing evaluation and rehabilitation as clinically indicated 6.Smoking cessation and alcohol counseling as clinically indicated P2 6

7 二診斷共識 Diagnosis and Pre-treatment evaluation of Nasopharynx Cancer 鼻咽癌之診斷及治療前評估 Workup (Pre-treatment evaluation) H&P Nasopharyngeal exam and biopsy Chest imaging CT with contrast and/or MRI with contrast of primary and neck PET-CT (option) Nutrition, speech and swallowing evaluation Dental evaluation as indicated Bone Scan Abdominal echo Multidisciplinary consultation as indicated 7

8 三治療共識鼻咽癌第一期原則上單獨使用放射治療, 即可達到不錯的局部控制及存活率, 局部晚期鼻咽癌第二三四期的治療方式同步性化學放射治療為主 (concurrent chemoradiation) 加輔助性化學治療 (adjuvant chemotherapy); 或是前導性化學治療 (Induction chemotherapy) 加同步性化學放射治療 (concurrent chemoradiation) 或放射治療 (radiotherapy) 鼻咽癌病患病遠端轉移時的主要治療為化學治療 (chemotherapy) 或是同步性化學放射治療 (concurrent chemoradiation) 8

9 四追蹤共識 Follow-up evaluation 治療後追蹤評估 1.Physical examination (1)Year 1 every 1-3 month (2)Year 2, every 2-6 month (3)Years 3-5, every 4-8 month (4)>5 years, every 12 month 2.Further reimaging as indicated based on signs/symptoms 3.Chest imaging as clinically indicated 4.Thyroid-stimulating hormone (TSH) every 6-12 mo if neck irradiated 5.Speech/hearing and swallowing evaluation and rehabilitation as clinically indicated 9

10 五鼻咽癌院內通用抗癌藥物處方最初出版日期 :95.03 最後更新日期 : 癌症類別 Neoadjuvant( 術前 ) Adjuvant( 術後 ) Palliative( 無法手術 ) 1. Cisplatin 60 mg/m 2 (N/S 500 c.c.; 4hrs ) + (5-FU 1000 mg/m 2 (N/S 500 c.c.; 3hrs ) + Leucovorin (LV) 100 mg (N/S 500 c.c.; 3hrs ) * 4 doses q 4 wks (Cancer 1984;53: ) 2.Cisplatin 60 mg/m 2 + UFUR mg/m 2 /d+lv (P.O.) 30mg/d q 4 wks ( 健保條例 ) 口腔癌口咽癌下咽癌鼻咽癌 3. (A) Cisplatin 60 mg/ m 2 + Bleomycin 8 mg/m 2 (N/S 100 c.c.; 30 mins) + 5-FU 1500 mg/ m 2 (N/S 500 c.c.; 4hrs )+ LV 200 mg (N/S 500 c.c.; 4hrs ) ( 同上 2., v. 5-FU/LV 亦可以 oral UFUR 與 oral LV 取代) (B) Epirubicin 50 mg/m 2 (N/S 100 c.c.; 30 mins) + MTX 100 mg/m 2 (N/S 100 c.c.;1 hr ) (MTX 200 mg/ m 2, N/S 500 c.c.; 3 hrs; for high grade, extensive, multiple foci, R1 resection ) + 5-FU 1500 mg/ m 2 + LV 200 mg ( 同上 2., v. 5-FU/LV 亦可以 oral UFUR 與 oral LV 取代) (European Journal of Cancer 1993 Vol.29 pp ) 4.Cisplatin 60 mg/m 2 /4 wks + Docetaxel 35,40 mg/m 2 (N/S 100 c.c.; 1 hr)* II /4 wks + 5-FU/LV (dose 同上 1. or 5-FU 1500 mg/m 2 (N/S 500 c.c.; 4hrs ) + Leucovorin 200 mg (N/S 500 c.c.; 4hrs ) )* II /4 wks (JCO Nov );( 健保條例 ) 5.Cisplatin 60 mg/m 2 /4 wks + Docetaxel 35,40 mg/m 2 (N/S 100 c.c.; 1 hr) * II /4 wks + UFUR mg/m 2 /d + LV (P.O.) 30mg/d ( 健保條例 ) C/T for CCRT ( combined with R/T ): (A). Cisplatin 30 mg/ m 2 (B). 同上 1. or 2 (N/S 500 c.c.; 3hrs) q wk * 4-6 cycles (with R/T) (Cancer Nov ) ** 因應病情須要, 可考慮下列藥物 Erbitux 250mg/ m 2 / dose (N/S 100 c.c., 2 hrs) ( 健保條例 ) Etoposide mg/m 2 (N/S 500 c.c.; 3rs,divided or single dose) ( 視 performance 而定 ) (Am J Clin Oncol 1985 Oct;8(5):393-5) Ifosfamide 2 g / m 2 /d (N/S 500 c.c.; 24 hrs; C.I.) 3 days (Oncology 2003; 65 (suppl 2):37-43) MMC 8mg/m 2 /cycle (or 5mg/m 2 /dose) (Cancer Treatment Reviews 2001; 27:35-50) 10

11 六鼻咽癌放射線治療政策與程序指引 1. 目的 : 制定鼻咽癌放射治療指引與執行規範 2. 適用範圍 : 適用於根治性鼻咽癌病患之放射治療 3. 腫瘤分期 ( 依據 AJCC th edition) 4. 放射治療之適應症 (indication) : Staging T1N0M0 Radiotherapy alone T1, N1-3; T2-T4, any N Any T, any N, M1 Treatment 1. Neoadjuvant chemotherapy followed by RT or CCRT 2. Concurrent chemoradiotherapy (CCRT)+/-adjuvant chemotherapy 1. Chemotherapy RT or CCRT 2. CCRT 修改日期 : 模擬定位 : (1) 病人治療時需採端正仰躺姿勢, 將頭置於適當曲度的塑膠彎枕 (headrest) 使頸部伸展, 雙肩盡量下垂, 雙上肢對稱擺於身體兩側 (2) 放射治療師依上述姿勢以熱塑面具 (thermoplastic mask) 固定病人頭部 (3) 在電腦斷層掃描定位室, 請病患依原姿勢躺好後戴上固定模具 (4) 在病患之模具或皮膚上, 貼上金屬標記, 在影像上呈現中心點之位置 (5) 電腦斷層之掃描範圍及條件為由腦部至肺尖應包含眼眶鼻咽頸部, 切片厚度 2.5~5 毫米治療之掃描範圍及切片厚度條件, 可由主治醫師自行訂定 (6) 透過靜脈注射顯影劑, 可加強判讀腫瘤侵犯之範圍, 但如果病患腎功能差或有其他不適應症則除外 (7) 其他影像 : 可考慮安排磁振照影 (MRI), 或考慮安排正子及電腦斷層掃描影像 (PET/CT), 作為分期腫瘤圈選用 6. 治療體積定義 (Target Volume Definition) 及放射治療計畫規劃 (Radiation Therapy Planning) 11

12 (1) GTV (Gross tumor volume): 鼻咽部腫瘤頸部轉移淋巴結由 CT 影像臨床訊息 PET/CT 或 MRI 影像可判讀之主要腫瘤 (primary tumor) 及臨床上呈陽性之淋巴腺 ( 直徑大於 1 公分之腫瘤或含有壞死區域之腫瘤 ) 如果放射治療前做過化學治療時, 需考慮化學治療前腫瘤之侵犯範圍 (2) CTV (Clinical tumor volume): 包含 GTV 及腫瘤可能侵犯之範圍, 可分為 CTV1 及 CTV2 (a) CTV1: 包含原發腫瘤的 GTV 加上 0.3~1 公分之範圍與兩側頸部淋巴結 (level II~V) (b) CTV2: 為 CTV1 加上 0.3~1 公分之範圍 (3) PTV (Planning Target Volume): 考慮擺位誤差及內部器官移動, 放射治療計畫在 CTV2 周圍至少要加上 3~5 毫米之安全範圍來形成 PTV 如果 GTV 或 CTV 太靠近腦幹或脊索時, 安全範圍可縮小至 1 毫米 7. 治療劑量 (1) CTV1: 66 Gy (2.2 Gy/fraction) to Gy ( Gy/fraction) 如因腫瘤侵犯至腦部或太過於接近腦幹時, 可考慮 hyperfractionated radiotherapy: 一天兩次治療, 每次劑量 1.2Gy, 共 76.8 格德 /64 次治療 (2) CTV2: 一般給予劑量 60~63 格雷 ( Gy/fraction) (3) 預防性照射 : 給予 Gy (2.0 Gy/fraction) to Gy ( Gy/fraction) (4) 治療天數應由病況決定, 合理範圍為 45~56 天 (5) 治療次數與劑量仍需依照臨床醫師判斷, 以上僅供參考 8. 危急器官定義之劑量限制 : (1) 腦幹 (Brain stem): 最高劑量 < 54 Gy (2) 脊索 (Spinal cord) : 最高劑量 < 45 Gy (3) 唾液腺 (Parotid Glands): 劑量限制為至少符合以下其中一個條件 : a. 平均劑量 < 26 Gy( 至少有一側之唾液腺符合 ); b. 至少兩側唾液腺 20 cc 之體積接受 < 20 Gy; c. 中值劑量 (median dose) < 30 Gy( 至少一側唾液腺符合 ) (4) 下頜骨 (Mandible) 顳下頜關節 (TMJ) : 最高劑量 < 70Gy (5) 聲帶 (Glottic Larynx) : 平均劑量 < 45 Gy (6) 視神經及視神經交义 : 最高劑量 < 55 Gy 12

13 (7) 眼球 : 最高劑量 < 45 Gy (8) 水晶體 : 最高劑量 < 10 Gy 9. 治療驗證 (Treatment Verification) (1) 三度空間放射治療或強度調控放射治療或銳速刀 : 治療前由放射師拍攝正交之驗證片 (orthogonal verification films) 來驗證照野之中心點 (2) 影像導引放射治療 (IGRT: OBI 或 CBCT): 如需要影像導引放射治療, 治療前應由放射師拍攝電腦斷層影像或正交之驗證片確認治療範圍, 治療期間應由醫師決定再次驗證的時間及頻率 13

14 七參考資料 ( 一 ) 診療指引參考文獻 1. NCCN Clinical Practice Guidelines in Oncology-Version Cancer of the Nasopharynx 2. 國家衛生研究院台灣癌症臨床研究合作組織 - 鼻咽癌臨床診療指引 (2011 年 12 月 ) ( 二 ) 抗癌藥物處方參考文獻 1. Cancer 1984;53: European Journal of Cancer 1993 Vol.29 pp JCO Nov Cancer Nov Am J Clin Oncol 1985 Oct;8(5): Oncology 2003; 65 (suppl 2): Cancer Treatment Reviews 2001; 27: Laramore GE, Scott CB, al-sarraf M et al. Adjuvant chemotherapy for resectable squamous cell carcinomas of the head and neck: report on Intergroup Study Int J Radiat Oncol Biol Phys 1992;23(4): Chang PM, Chen PM, Chu PY et al. Effectiveness of pharmacokinetic modulating chemotherapy combined with cisplatin as induction chemotherapy in resectable locally advanced head and neck cancer: phase II study. Cancer Chemother Pharmacol 2008;63(1): Vermorken JB, Trigo J, Hitt R et al. Open-label, uncontrolled, multicenter phase II study to evaluate the efficacy and toxicity of cetuximab as a single agent in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck who failed to respond to platinum-based therapy. J Clin Oncol 2007;25(16): Taylor SG, McGuire WP, Hauck WW, Showel JL, Lad TE. A randomized comparison of high-dose infusion methotrexate versus standard-dose weekly therapy in head and neck squamous cancer. J Clin Oncol 1984;2(9): Woods RL, Fox RM, Tattersall MH. Methotrexate treatment of squamous-cell head and neck cancers: dose-response evaluation. Br Med J (Clin Res Ed) 1981;282(6264): Colevas AD. Chemotherapy options for patients with metastatic or recurrent squamous cell carcinoma of the head and neck. J Clin Oncol 2006;24(17): Forastiere AA, Shank D, Neuberg D, Taylor SG, DeConti RC, Adams G. Final report of a phase II evaluation of paclitaxel 14

15 in patients with advanced squamous cell carcinoma of the head and neck: an Eastern Cooperative Oncology Group trial (PA390). Cancer 1998;82(11): Forastiere AA, Metch B, Schuller DE et al. Randomized comparison of cisplatin plus fluorouracil and carboplatin plus fluorouracil versus methotrexate in advanced squamous-cell carcinoma of the head and neck: a Southwest Oncology Group study. J Clin Oncol 1992;10(8): Kohno N, Ichikawa G, Nakazawa E, Kusunoki M, Nishiya M. Induction chemotherapy with cisplatin, etoposide, and mitomycin-c (PEM) regimen in advanced cases with cancer of pharynx and oral cavity. Auris Nasus Larynx 1995;22(1): Posner MR, Hershock DM, Blajman CR et al. Cisplatin and fluorouracil alone or with docetaxel in head and neck cancer. N Engl J Med 2007;357(17): Pointreau Y, Garaud P, Chapet S et al. Randomized trial of induction chemotherapy with cisplatin and 5-fluorouracil with or without docetaxel for larynx preservation. J Natl Cancer Inst 2009;101(7): Vermorken JB, Remenar E, van HC et al. Cisplatin, fluorouracil, and docetaxel in unresectable head and neck cancer. N Engl J Med 2007;357(17): Kish JA, Weaver A, Jacobs J, Cummings G, Al-Sarraf M. Cisplatin and 5-fluorouracil infusion in patients with recurrent and disseminated epidermoid cancer of the head and neck. Cancer 1984;53(9): Hainsworth JD, Spigel DR, Greco FA et al. Combined modality treatment with chemotherapy, radiation therapy, bevacizumab, and erlotinib in patients with locally advanced squamous carcinoma of the head and neck: a phase II trial of the Sarah Cannon oncology research consortium. Cancer J 2011;17(5): Kundu SK, Nestor M. Targeted therapy in head and neck cancer. Tumour Biol 2012;33(3): Morton RP, Rugman F, Dorman EB et al. Cisplatinum and bleomycin for advanced or recurrent squamous cell carcinoma of the head and neck: a randomised factorial phase III controlled trial. Cancer Chemother Pharmacol 1985;15(3): Zhang L, Zhang Y, Huang PY, Xu F, Peng PJ, Guan ZZ. Phase II clinical study of gemcitabine in the treatment of patients with advanced nasopharyngeal carcinoma after the failure of platinum-based chemotherapy. Cancer Chemother Pharmacol 2008;61(1): Burtness B. Commentary: bevacizumab and erlotinib with chemoradiation for head and neck cancer. Cancer J 2011;17(5): Preliminary results of a randomized trial comparing neoadjuvant chemotherapy (cisplatin, epirubicin, bleomycin) plus radiotherapy vs. radiotherapy alone in stage IV(> or = N2, M0) undifferentiated nasopharyngeal carcinoma: a positive effect on progression-free survival. International Nasopharynx Cancer Study Group. VUMCA I trial. Int J Radiat Oncol 15

16 Biol Phys 1996;35(3): Onat H, Basaran M, Esassolak M et al. High-dose epirubicin and cisplatin in locally advanced undifferentiated nasopharyngeal carcinoma. Clin Oncol (R Coll Radiol ) 2002;14(6): Shiu WC, Tsao SY. Etoposide (VP16-213) in the treatment of advanced nasopharyngeal carcinoma. Eur J Cancer Clin Oncol 1988;24(4): He XY, Hu CS, Ying HM, Wu YR, Zhu GP, Liu TF. Paclitaxel with cisplatin in concurrent chemoradiotherapy for locally advanced nasopharyngeal carcinoma. Eur Arch Otorhinolaryngol 2010;267(5): Wei WH, Cai XY, Xu T et al. Concurrent weekly docetaxel chemotherapy in combination with radiotherapy for stage III and IVA-B nasopharyngeal carcinoma. Asian Pac J Cancer Prev 2012;13(3): 頭頸癌化療處方集說明 102 年 7 月 31. Cisplatin 60-75mg/m 2 + (5-FU 1000 mg/m 2 + Leucovorin (LV) mg) *4 days q3-4 wks 若病人不願住院, 只在門診化療室接受治療, 則上述 regimen 可修正為 : Cisplatin 60-75mg/m FU mg/m 2 + Leucovorin (LV) mg q3-4 wks 32. Cisplatin 60-75mg/m 2 + oral (UFUR mg/m 2 /d + LV 30 mg/d * 3 - ~4 - wks q3-4 wks 依據 : JCO 1992;10: R.R.:(CF:carboplatin + 5-FU) MTX (PF:Cisplatin + 5-FU) > MTX median response duration; median survival time similar in CF,PF, MTX 可見 MTX 於 HNSCC 角色相當重要 Eur J Cancer 1993; 29A(5):704-8 Epirubicin, MTX and bleomycin in the recur. HNSCC (R.R.:44%) Epirubicin, MTX, Bleomycin 亦為 active agents in HNSCC Annals of Oncology (2010) 21 (Supp7) Educational Book of the 35 th ESMO Congress Milan Oct.2010 * Of large number of conventional single agents in p ts with recur. /meta. HNSCC, the four most active and most extensively 16

17 used agents are MTX, cisplatin, 5-FU and bleomycin. 由此, 亦可觀察到 Epirubicin, MTX, Bleomycin 於 HNSCC 角色相當重要將 Epirubicin, MTX, Bleomycin 納入 PF 之 backbone regimen, 且為避免門診化療給藥時間過長及 serious side effects 可採取 biweekly (A)<-> (B) regimen 33.(A) Cisplatin 60-75mg/ m 2 + Bleomycin 8(6-10) mg/ m 2 +5-FU mg/ m 2 + LV mg ( 同上 2., 亦可以 oral UFUR 與 oral LV 取代 v. 5-FU+LV) (B) Epirubicin 50 mg/ m 2 +MTX 60 mg/ m 2 (or mg/ m 2 for high grade, extensive, multiple foci, R1 resection ) +5-FU mg/ m 2 +LV mg) 同上 2., 亦可以 oral UFUR 與 oral LV 取代 v. 5-FU+LV * 增列 Taxotere: 又依據 : Ai Zheng 2003 Aug; 22(8) :877-9 TPF ( Taxotere + Cisplatin + 5-FU) in induction C/T for HNSCC C.R.: 24% P.R.: 48% (R.R.:72%) R.R. (oral cancer):63.6%; R.R.(others; tongue, larynx, hypopharynx, N-P):71.4% Medscape Oncology 2006; 9(2) In reur./meta. HNSCC: PFS: PF:8.2 months ; TPF: 11 months ORR: PF:6.4% ; TPF: 72% Educational Book of the 35th ESMO Congress Milan, Oct,2010 亦有提及 : ORR: Cisplatin + Taxol(27%) PF(26%) TPF(Taxotere, Cisplatin, 5-FU): 44% (median time to progression: 7.5 mothers ; median OS: 11 months) 可見 MTX( 前述 4 篇文章 ) 與 Taxotere, 除了 PF 之外, 於 HNSCC 相當重要 17

18 p.s. 依據本院至統計 104 位病人僅列 neoadjuvant, adjuvant & CCRT alone 三類典型治療模式中之代表疾病 ( 各個疾病治療之詳情為了節省篇幅不一一列出 ) *neoadjuvant C/T (13p ts, oral cavity cancers) C.R.+ P.R. :61.5%(8/13) (tumor resection rate) Tumor control rate : 92.3% (12/13) P.D.: 7.8% (1/13) * adjuvant C/T (median overall survival): oral cavity cancers (29 p ts ):1183 days oropharyngeal cancer (3p ts ):1529days * CCRT (NPC): C.R.:66.7% (12/18); P.R.:5.6% (1/18) S.D.:11.1%(2/18) P.D.:16.7%(3/18) 癌登資料庫 ( 年 ) NPC 本院全國 oropharynx 本院全國 5- yr survival of O-P 1- yr(%) yr(%) Stage 本院 AJCC 2- yr(%) yr(%) I 0.0% 72.6% 3- yr(%) yr(%) II 100% 58.0% 4- yr(%) yr(%) III 50% 45.0% 5- yr(%) yr(%) 沒有資料沒有資料 IV 0.0% 32.4% 18

19 oral cavity cancers: 1- yr survival of rate(%) 2- yr survival of rate(%) 3- yr survival of rate(%) Stage 本院 AJCC Stage 本院 AJCC Stage 本院 AJCC I I I II II II III III III IV IV IV yr survival of rate(%) 5- yr survival of rate(%) Stage 本院 AJCC Stage 本院 AJCC I I II II III III IV IV NPC 及 oral cavity cancers 之 1-5 yr survival rate 與癌登全國資料庫相比, 高出些許, 而 oropharyngeal cancer 則相似, 由上述資料, 顯見 long- term survival of HNSCC 在全體同仁之盡心協力合作之下, 本院治療之效果些略高於全國或 global 平均資料, 但由於個案量不多, 尚未足以下結論健保條例 (from 100/1, for unresectable, locally advanced HNSCC) 34. Taxotere 60-75mg/ m 2 + Cisplatin 60-75mg/m 2 + (5-FU 1000 mg/m 2 + Leucovorin (LV) mg) *4 days q3-4 wks 35. Taxotere 60-75mg/ m 2 + Cisplatin 60-75mg/m 2 + oral (UFUR mg/m 2 /d + LV 30 mg/d * 3 - ~4 - wks q3-4 wks * 加入 MTX 保留 (4) or (5) backbone regimen, 但根據院內統計資料 (100/1-102/5), 治療效果與 TPF 大致類似 ( 統計資料說明見下頁 ), 故自 102/7 起,Taxotere- containing regimen 不再加入 MTX : 19

20 但為避免門診化療給藥時間過長及 serious side effects 可採取 biweekly (A)<-> (B) regimen 36.(A) Cisplatin 60-75mg/ m 2 + Taxotere mg/ m FU mg/ m 2 +LV mg ( 亦可以 oral UFUR 與 oral LV 取代) (B) Taxotere 35-50mg/ m 2 +5-FU mg/ m 2 +LV mg ( 亦可以 oral UFUR 與 oral LV 取代) 因應病情須要, 可考慮下列藥物 Avastin 5mg/kg/dose Erbitux 250mg/ m 2 / dose Etoposide mg/ m days ( 視 performance 而定 ) Ifosfamide g/ m 2 / d 3days q 4-6wks Gemzar mg/ m 2 / dose ( 三 ) 放射治療指引參考文獻 1. NCCN guidelines in oncology-2018 Version Wu Q, Manning M, Schmidt-Ullrich R, Mohan R. The potential for sparing of parotids and escalation of biologically effective dose with intensity-modulated radiation treatments of head and neck cancers: a treatment design study. Int J Radiat Oncol Biol Phys 2000;46(1): Dogan N, King S, Emami B, et al. Assessment of different IMRT boost delivery methods on target coverage and normal-tissue sparing. Int J Radiat Oncol Biol Phys 2003;57(5): Mohan R, Wu Q, Morris M, et al. Simultaneous Integrated Boost (SIB) IMRT of advanced head and neck squamous cell carcinomas dosimetric analysis. Int J Radiat Oncol Biol Phys 2001;51(3): M. Johnston, S. Clifford, R. Bromley, M. Back, L. Oliver, T. Eade. Volumetric-modulated arc therapy in head and neck radiotherapy: a planning comparison using simultaneous integrated boost for nasopharynx and oropharynx carcinoma. Clin Oncol 2011:23(8):

21 6.Lin JC, Jan JS, Hsu CY, et al. Phase III study of concurrent chemoradiotherapy versus radiotherapy alone for advanced nasopharyngeal carcinoma: positive effect on overall and progression-free survival. J ClinOncol Feb 15;21(4): Chan AT, Leung SF, Ngan RK, et al. Overall survival after concurrent cisplatin-radiotherapy compared with radiotherapy alone in locoregionally advanced nasopharyngeal carcinoma. J Natl Cancer Inst 2005;97: Al-Sarraf M, LeBlanc M, Giri PG, et al. Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: phase III randomized Intergroup study J ClinOncol 1998;16: Wee J, Tan EH, Tai BC, et al. Randomized trial of radiotherapy versus concurrent chemoradiotherapy followed by adjuvant chemotherapy in patients with American Joint Committee on Cancer/International Union Against Cancer Stage III and IV nasopharyngeal cancer of the endemic variety. J ClinOncol 2005;23:

2013

2013 鼻咽癌診療指引頭頸癌多專科團隊擬定 2010.01.27 初訂 2011.03.23 修訂 2012.03.28 修訂 2013.03.27 修訂前言鼻咽癌, 乃中國人特有之癌症根據統計, 男性每十萬人每年罹患鼻咽癌的人數在台灣是 7.7 人美國 0.63 人日本 0.27 人即使移居美國的第二代中國人也比當地白人罹患率多 7 倍一般而言, 男性比女性易患鼻咽癌, 其比例約 3 比