高雄榮民總醫院 鼻咽癌診療原則 提醒您：此份診療原則為本院關於癌症診斷與治療之參考指引。臨 床應用上可能會依照個人情況而有所調整。歡迎與您的醫師討論。 [ 2016 年第 1 版 ] 頭頸癌治療團隊制訂

與上一版的差異 化療藥物 Regimen 及給予方式單純化 強調 surgery 在 early residual disease 狀態 的角色 釐清 Induction CT 的使用時機

Carcinoma of Nasopharynx WORK-UP History & PE Biopsy & Pathology Image  MRI and/or CT of H & N  Chest X-ray  Bone scan  Abd. Sono  ± PET scan EBV status: viral load, ± EB- EA/NA, ± EB-VCA IgG/IgA Dental evaluation  Panorex ± teeth extraction Hearing evaluation  PTA, tympanogram Multidisciplinary consultation STAGING & TREATMENT TREATMENT [T1, N0, M0] Definitive RT [T1, N1-3, M0] or [T2-4, any N, M0] 詳見 Page 2 [Any T, any N, M1] 詳見 Page 3FOLLOW-UP [Post-Tx 3-6 months]  Baseline MRI and/or CT [0-3 years after Tx]  Every 2-3 months: PE, nasopharyngoscopy  Every 6-12 months: viral load, ± EB-EA/NA, ± EB- VCA IgG/IgA; MRI ± CT, CxR, bone scan & Abd. Sono as indicated [ 4-5 years after Tx]  Every 4-6 months: PE, nasopharyngoscopy [ 5 years later after Tx]  Every 6-12 months: PE, nasopharyngoscopy 高雄榮民總醫院 臨床診療指引 Ver.1 修訂於 Page 1 (Ref. 1)

Carcinoma of Nasopharynx Primary treatment CCRT ± Adjuvant CT 註 1-3 High risk for distant failure (clinical cT4 or cN3) 建議加 打 2-3 courses of adjuvant CT 。 Induction CT + CCRT or RT 註 courses for locally advanced cT4 ；若只打 1 cycle 且 與後續 CCRT 間隔小於 2 weeks ，視為 CCRT only 。 高雄榮民總醫院 臨床診療指引 Ver.1 修訂於 Page 2 (Ref. 1) ＃ Salvage neck dissection is indicated if residual neck disease. ＊ Salvage nasopharyngectomy is indicated for operable residual primary tumor. Definitive RT 註 1 Poor medical condition or patient’s preference 。 Follow-up Surgery if operable ＊ ＃ Complete clinical response Residual disease or clinically suspicious residue Response and salvage treatment Clinical T1, N1-3 or T2-4, any N, M0 Adjuvant CT 註 3

Carcinoma of Nasopharynx Primary treatment Platinum-based combination CT ± RT or CCRT 註 1-3 CCRT 註 1-2 高雄榮民總醫院 臨床診療指引 Ver.1 修訂於 Page 3 (Ref. 1) Follow-up Complete clinical response Residual disease Palliative CT 註 3 Palliative RT 註 1 Adjuvant treatment Definitive RT 註 1 Poor medical condition or patient’s preference Any T, any N, M1 Supportive care Surgery if applicable

Carcinoma of Nasopharynx Principles of Radiotherapy Definitive Radiotherapy Primary and gross adenopathy ： Gy (2.0 Gy/fraction) Neck uninvolved nodal stations ： Gy ( Gy/fractions) CCRT or RT RT alone if ： Old age, Impaired renal function, Poor condition Palliative RT Indicated in ： Relieve local symptoms, Prevent debilitation such as spinal cord compression and pathological fracture, Achieve durable locoregional control. 高雄榮民總醫院 臨床診療指引 Ver.1 修訂於 Page 4 (Ref. 1,5,6) 註1註1

Carcinoma of Nasopharynx Principles of Chemotherapy Regimen 1: q3w CDDP ± Cetuximab + RT 註 4 Cisplatin (80-100mg/ m2) q3w during R/T Cetuximab(400mg/ m2) loading dose first week, then Cetuximab(250mg/ m2) maintain dose D1 + Cisplatin (80-100mg/ m2) q3w D2 during R/T Regimen 2: Weekly CDDP ± Cetuximab + RT 註 4 Cisplatin (30-40mg/ m2) weekly during R/T Cetuximab(400mg/ m2) loading dose first week, and then Cisplatin (30-40mg/ m2) weekly D1 + Cetuximab(250mg/ m2) maintain dose D2 during R/T Regimen 3: q3w Carboplatin ± Cetuximab + RT 註 4 Carboplatin (AUC x 5mg) q3w during R/T Cetuximab(400mg/ m2) loading dose first week, then Cetuximab(250mg/ m2) maintain dose D1 + Cisplatin (80-100mg/ m2) q3w D2 during R/T Regimen 4: Weekly Cetuximab + RT 註 4 Cetuximab(400mg/ m2) loading dose first week, then Cetuximab(250mg/ m2) maintain dose during RT Concurrent with RT 高雄榮民總醫院 臨床診療指引 Ver.1 修訂於 Page 5 (Ref. 1,5-9) 註2註2

Carcinoma of Nasopharynx Regimens of Chemotherapy Regimen 1: q3-4 weeks CDDP ± F ± weekly Cetuximab 註 4 Cisplatin (20mg/ m2) D1-D5 Fluorouracil (5-FU) (1000mg/m2) D1-D5 Cetuximab(400mg/ m2) loading dose first week, then weekly Cetuximab (250mg/ m2) Regimen 2: q3-4 weeks CDDP ± F ± weekly Cetuximab 註 4 Cisplatin(80-100mg/ m2) D1 Fluorouracil (5-FU) (1000mg/ m2) D2-D5 Cetuximab(400mg/ m2) loading dose first week, then weekly Cetuximab (250mg/ m2) Regimen 3: q3-4 weeks Carboplatin ± F ± weekly Cetuximab 註 4 Carboplatin (AUC x 5mg) D1 Fluorouracil (5-FU) (1000mg/ m2) D2-D5 Cetuximab(400mg/ m2) loading dose first week, then weekly Cetuximab (250mg/ m2) Induction, salvage or adjuvant, 建議 2-3cycles 高雄榮民總醫院 臨床診療指引 Ver.1 修訂於 Page 6 (Ref. 5-8) 註3註3

Carcinoma of Nasopharynx Regimens of Chemotherapy Regimen 4: q3-4 weeks T + P ± F ± weekly Cetuximab Taxotere(60 mg/ m2) D1 註 4 Cisplatin(60-75 mg/ m2) D1 Fluorouracil (5-FU)( mg/m2) D2-D5 Cetuximab (400mg/ m2) loading dose first week, then Cetuximab (250mg/ m2) maintain dose Regimen 5: weekly Cetuximab 註 4 Cetuximab (400mg/ m2) loading dose first week, then Cetuximab (250mg/ m2) maintain dose Regimen 6: oral Fluorouracil Ufur cap (tegafur 100mg+uracil 224mg) 2# TID (Salvage or palliative CT 中作為取代 iv-formed 5-FU 之替代藥物 ) Induction, salvage or adjuvant, 建議 2-3cycles 高雄榮民總醫院 臨床診療指引 Ver.1 修訂於 Page 7 (Ref. 5-12) 註3註3

Carcinoma of Nasopharynx Regimens of Chemotherapy Regimen 7: q4w GGGP Gemcitabine (1000mg/ m2) D1, 8, 15 Cisplatin (60mg/m2) D22 Regimen 8: P-FL Cisplatin (60mg/ m2) week 1, 3, 5, 7 Fluorouracil (5-FU)(2500mg/ m2) + Leucovorin (250mg/m2) mixed week 2, 4, 6, 8 Induction, salvage or adjuvant, 建議 2-3cycles 高雄榮民總醫院 臨床診療指引 Ver.1 修訂於 Page 8 (Ref. 5-12) 註3註3

Carcinoma of Nasopharynx 特殊用藥健保給付規定 Taxotere 頭頸部癌，限局部晚期且無遠端轉移之頭頸部鱗狀細胞癌且無法手術切除者。 與 Cisplatin 及 5-FU 併用，作為放射治療前的引導治療，限使用四個療程。 Cetuximab 限與放射線療法合併使用於局部晚期之口咽癌、下咽癌及喉癌患者，且符合下列條 件之一： 1. 年齡 ≧ 70 歲 2.Ccr ＜ 50ml/min 3. 聽力障礙者 ( 聽力障礙定義為 500Hz 、 1000Hz 、 2000Hz 平均聽力損失大於 25 分貝 ) 4. 無法耐受 platinum-based 化學治療。 使用總療程以接受 8 次輸注為上限。 需經事前審查核准後使用。 Carboplatin 限腎功能不佳 (CCr < 60) 或曾作單側或以上腎切除之惡性腫瘤患者使用。 高雄榮民總醫院 臨床診療指引 Ver.1 修訂於 Page 9 註4註4

Carcinoma of Nasopharynx References 1.NCCN Clinical Practice Guidelines in Oncology – Head and Neck Cancers Version Lee SW, Nam SY, Im KC, et al. Prediction of prognosis using standardized uptake value of 2-[(18)F] fluoro-2-deoxy- d- glucose positron emission tomography for nasopharyngeal carcinomas. Radiother Oncol 2008;87:211– Chan SC, Chang JT, Wang HM, et al. Prediction for distant failure in patients with stage M0 nasopharyngeal carcinoma: The role of standardized uptake value. Oral Oncol 2009;45: 52–58. 4.Wen-Shan Liu, Ming-Fang Wu, Hsien-Chun Tseng, Jung-Tung Liu, Jui-Hung Weng, Yueh-Chun Lee, Jong-Kang Lee. The role of pre-treatment FDG PET in nasopharyngeal carcinoma treated with intensity-modulated radiotherapy. Int. J. Radiat. Oncol. Biol. Phys (2): Chua DT, Ma J, Sham JS et al (2005): Long-term survival after cisplatin-based chemotherapy and radiotherapy for nasopharyngeal carcinoma: a pooled data ananlysis of two phase III trialsl J Clin Oncol 23: Al-Amro A, Al-Rajhi N, Khafaga Y et al. (2005): Neoadjuvant chemotherapy followed by concurrent chemo-radiation therapy in locally advanced nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys 62: Chan AT, Ma BB, Lo YM et al. (2004): Phase II study of neoadjuvant carboplatin and paclitaxel followed by radiotherapy and concurrent cisplatin in patients with locoregionally advanced nasopharyngeal carcinoma: therapeutic monitoring with plasma Epstein-Barr virus DNA. J Clin Oncol 22: Johnson FM, Garden Asm Oakner HK et ak, (2005): A phase I/II study of enoadjuvant chemotherapy followed by radiation with boost chemotherapy for advance T-stage nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys 63: Chan AT, Leung SF, Ngan RK et al. (2005): Overall survival after concurrent cisplatin-radiotherapy compared with radiotherapy alone in locoregionally advanced nasopharyngeal carcinoma. J natl Cancer Inst 97: Hong RL, Ting LL, Ko JY, et al. Induction Chemotherapy With Mitomycin, Epirubicin, Cisplatin, Fluorouracil, and Leucovorin Followed by Radiotherapy in the Treatment of Locoregionally Advanced Nasopharyngeal Carcinoma. J Clin Oncol 19: , Ma BB, Tannock IF, Pond GR, et al. Chemotherapy with gemcitabine-containing regimens for locally recurrent or metastatic nasopharyngeal carcinoma. Cancer. 2002; 95: 2516– Lin JC, Jan JS, Chen KY, et al. Outpatient weekly 24-hour infusional adjuvant chemotherapy of cisplatin, 5-fluorouracil, and leucovorin for high-risk nasopharyngeal carcinoma. Head Neck 2003;25:438–450. 高雄榮民總醫院 臨床診療指引 Ver.1 修訂於 Page 10