峯 ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) 106 10 25 /
頭頸癌診療指引 106 : 105 106-2 -1 1. 2. * 1. ( / ) 2.*consider re-resection to achieve negative margins for positive resection margins if feasible T4 or N3a T4or N3 EBV DNA 癌症診療指引128
口腔癌診療指引共識1-1 Selected T1N0 Lip/oral cancer ( ) ( ) *1 *3 T1-2,N0 T3-T4,N0 or Any T,N1-3 ( ) + pn0 pn(+) ( ) *2 *1 *3 *1 (N2 or N3 nodal disease) (pt3 or pt4 癌症診療指引129 primary) (nodal disease in Levels IV or V) ( ) Type V - WPOI *2 T1-T2,N1 OBS or RT T1-T2 *3 consider re-resection to achieve negative margins for positive resection margins if feasible
口腔癌診療指引共識2 ) -2 ( ) ( 癌症診療指引130
口腔癌診療指引共識檢查內容 ( ) ( ) ( ) ( / ) 癌症診療指引131
下咽癌診療指引共識1-1 ( ) ( ) ( ) ( ) (advanced T status is indicated) T1-2, N0-3 (adequae Laryngeal function) + + * * LN 6cm central necrosis 癌症診療指引132 consider re-resection to achieve negative margins for positive resection margins if feasible
下咽癌診療指引共識2 * -2 + T3 any N level VI ( ) * 癌症診療指引133
下咽癌診療指引共識3 any N T4a -3 level VI ( ) * * (laryngectomy required) ( ) 癌症診療指引134 + consider re-resection to achieve negative margins for positive resection margins if feasible
口咽癌診療指引共識1 * -1 (P 16) ( ) ( / ) ( ) ( ) T1-2 N0-1 ( ) (for N0) (for N1) * consider re-resection to achieve negative margins for positive resection margins if feasible 癌症診療指引135
口咽癌診療指引共識2 T3-4N0-2 ( ) * * Any T N2-3 + ( ) 癌症診療指引136 LN 6cm central necrosis consider re-resection to achieve negative margins for positive resection margins if feasible
喉癌診療指引共識1-1 ( ) ( / ) ( ) T1or Tis N0 T2N0 * * 癌症診療指引137 ( ) (advanced T status is indicated) consider re-resection to achieve negative margins for positive resection margins if feasible
喉癌診療指引共識2 T3 an y N -2 + * * 癌症診療指引138
喉癌診療指引共識3-3 T4a any N ( ) + 癌症診療指引139 + * * + consider re-resection to achieve negative margins for positive resection margins if feasible
T1N0 鼻咽癌診療指引共識1-1 ( ) ( ) ( ) EBV DNA T1,N1-3; T2-T4,any N Any T Any N M1 * + + 癌症診療指引140 * T4 or N3a
頭頸癌診療指引追蹤流程 3 3-6 3 6-12 3 3-6 3 6-12 癌症診療指引141
頭頸癌診療指引 參考文獻 1. Al-Sarrf M, LeBlanc M, Giri PG, et al. Chemotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer : phase III randomized Intergroup study 0099. J Clin Oncol 1998; 16:1310-1317.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 Clin Oncol 2005; 23 : 6730-6738. 2. Bernier J, Cooper JS, Pajuk TF, et al. Defining risk levels in locally advanced head and neck cancers : A comparative analysis of concurrent postoperative radiation plus chemotherapy trials of the EORTC (#22931) and RTOG (#9501).Head Neck 2005; 27: 843-850. 3. Bernier J, Domenge C, Ozsahin M et al. Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer.n Engl J Med 2004; 350:1945-1952. 4. Budach W, Hehr T, Budach V, et al. A meta-analysis of hyperfractionated and accelerated radiotherapy and combined chemotherapy and radiotherapy regimens in unresected locally advanced squamous cell carcinoma of the head and neck. BMC Cancer 2006; 6 : 28-38. 5. Chan AT, Leung SF, Ngan RK, et al. Overall survival after concurrent cisplatin-radiotherapy comparedwith radiotherapy alone in locoregionally advanced nasopharyngeal carcinoma.j Natl Cancer Inst 2005; 97: 536-539. 6. Chan ATC, Hsu M-M, Goh BC, et al. Multicenter, phase II study of cetuximab in combination with carboplatin in patients with recurrent or meta tatic nasopharyngeal carcinoma.j Clin Oncol 2005; 23: 3568-3576. 7. Cooper JS, Pajak TF, Forastiere AA et al. Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcfinoma of the head and neck.n Engl J Med 2004; 350(19) : 1937-1944. 8. Hartford AC, Palosca MG, Eichler TJ, et al. American Society for Therapeutic Radiology and Oncology (ASTRO)and American College of Radiology (ACR) Practice Guidelines for Intensity-Modulated Radiation Therapy (IMRT).Int J Radiat Oncol Biol Phys 2009; 73: 9-14. 9. NCCN Head abd Neck Cancer Guidelines Version 2.2017. 癌症診療指引142
頭頸癌診療指引 參考文獻 10. Machtay M, Moughan J, Trotti A, et al. Factors associated with severe late toxicity after concurrent chemoradiation for locally advanced head and neck cancer : an RTOG analysis.j Clin Oncol 2008; 26 : 3582-3589. 11. Sanguineti G, Geara FB, Garden AS, et al. Carcinoma of the nasopharynx treated by radiotherapy alone : determinants of local and regional control.int J Radiat Oncol Biol Phys 1997; 37: 985-996. 癌症診療指引143
癌症診療指引144 Squamous Cell Cancers Lip, Oral Cavity, Oropharynx, Hypopharynx, Glottic Larynx, Supraglottic Larynx, Ethmoid Sinus, Maxillary Sinus, Occult Primary Primary systemic therapy + concurrent radiotherapy mg/m 2 Cisplatin 75-100 1 Q3W 3 with RT 1, 2 mg/m 2 Cetuximab 400* 250 1 QW 8 3 *1st dose 400 mg/m2 then followed by 250 mg/m2 mg/m 2 Carboplatin 70 1-4 Q3W 3 with RT 4 5-FU 600 1-4 Q3W 3 with RT mg/m 2 Carboplatin 70 1-5 Q4W 2 with RT 5 5-FU 600 1-5 Q4W 2 with RT
mg/m2 癌症診療指引145 5-FU 600 1-5 Q2W 6 with RT 6 Hydroxyurea 1g PO Q12H 11 doses Q2W 6 with RT mg/m 2 Paclitaxel 30 1 QW 7 6 Cisplatin 20 2 QW 7 mg/m 2 Paclitaxel 175 1 Q3W Min 6 18 Cisplatin 75 1 Q3W Min 6 mg/m 2 Cisplatin 60-100 1 Q3W 3 with RT 7 5-FU 800-1000 1-5 Q3W 3 with RT mg/m 2 Cisplatin 60 1 Q2W 7 with RT 7 5-FU 800 1-5 Q2W 7 with RT mg/m 2 Cisplatin 20 1-4 Q4W 2 with RT 19 5-FU 1000 1-4 Q4W 2 with RT
mg/m2 癌症診療指引146 Cisplatin 60-100 1 Q3W Min 6 18 5-FU 600-1000 1-4 Q3W Min 6 mg/m 2 Carboplatin 100 1 QW 8 8 Paclitaxel 40-45 1 QW 8 mg/m 2 Cisplatin 20-40 1 QW 4 9 mg/m 2 Cisplatin 40 1 QW 4 10 mg/m 2 Carboplatin 25 1-5 QW 5 with RT 16 mg/m 2 Cetuximab 400* 250 1 QW # 17 Cisplatin 60-100 1 Q3W *1 st dose 400 mg/m 2 then followed by 250 mg/m 2 #1 st cycle before RT and continued cycles during RT
mg/m2 癌症診療指引147 Cisplatin 50 1 Q2W 6 31 UFUR 800 mg* PO QD 1-14 Q2W 6 Leucovorin 60 mg PO QD 1-14 Q2W 6 Postoperative Chemoradiation *Or 300 mg/m2 mg/m 2 Cisplatin 75-100 1 Q3W 3 with RT 11-13, 15 mg/m 2 Cisplatin 25-50 1 QW 7-9 with RT 14 mg/m 2 Cetuximab 400* 250 1 QW # 20 Cisplatin 30 1 QW # *1 st dose 400 mg/m 2 then followed by 250 mg/m 2 #1 st cycle before RT and continued cycles during RT mg/m 2 Cetuximab 400* 250 1 QW # 20 Docetaxel 15 1 QW # *1 st dose 400 mg/m 2 then followed by 250 mg/m 2 #1 st cycle before RT and continued cycles during RT
mg/m2 癌症診療指引148 Cisplatin 20 1-5 Q4W 2 21 5-FU 600 1-5 Q4W 2 Induction/Sequential chemotherapy mg/m 2 Docetaxel 60-75 1 Q3W 3-4 22, 24 Cisplatin 60-75 1 Q3W 3-4 5-FU 600-750 1-5 Q3W 3-4 mg/m 2 Docetaxel 60-75 1 Q3W 3 23 Cisplatin 60-100 1 Q3W 3 5-FU 750-1000* 1-4 # Q3W 3 *Continuous infusion for 24 h # May extend to day 5 if tolerable mg/m 2 Paclitaxel 175 1 Q3W 3 25 Cisplatin 100 2 Q3W 3 5-FU 500 2-6 Q3W 3
mg/m2 癌症診療指引149 Cisplatin 80-100 1 Q3W 2-4 26 5-FU 800-1000 3-5 Q3W 2-4 Following induction, agents to be used with concurrent chemoradiation typically include weekly carboplatin or cetuximab mg/m 2 Cisplatin 100 1 QW 6 with RT 27 mg/m 2 Carboplatin 1.5-2 AUC 1 QW 7 28 mg/m 2 Cetuximab 400* 250 1 QW 7 with RT 29 *1 st dose 400 mg/m 2 then followed by 250 mg/m 2 mg/m 2 Cisplatin 50 1 Q2W 6 30 UFUR 800 mg* PO QD 1-14 Q2W Leucovorin 60 mg PO QD 1-14 Q2W *Or 300 mg/m 2
癌症診療指引150 1. Forastiere AA, Zhang Q, Weber RS, et al. Long-term results of radiotherapyog 91-11: a comparison of three nonsurgical treatment strategies to preserve the larynx in patients with locally advanced larynx cancer. J Clin Oncol 2013;31:845-852. 2. Adelstein DJ, Li Y, Adams GL, et al. An intergroup phase III comparison of standard radiation therapy and two schedules of concurrent chemoradiotherapy in patients with unresectable squamous cell head and neck cancer. J Clin Oncol 2003;21(1):92-98. 3. Bonner JA, Harari PM, Giralt J, et al. Radiotherapy plus cetuximab for locoregionally advanced head and neck cancer: 5-year survival data from a phase 3 randomised trial, and relation between cetuximab-induced rash and survival. Lancet Oncol 2010;11:21-28. 4. Denis F, Garaud P, Bardet E, et al. Final results of the 94-01 French Head and Neck Oncology and Radiotherapy Group randomized trial comparing radiotherapy alonewith concomitant radiochemotherapy in advanced-stage oropharynx carcinoma. J Clin Oncol 2004;22:69-76. 5. Bourhis J, Sire C, Graff P, et al. Concomitant chemoradiotherapy versus acceleration of radiotherapy with or without concomitant chemotherapy in locally advanced head and neck carcinoma (GORTEC 99-02): an open-label phase 3 randomised trial. Lancet Oncol 2012;13:145-153. 6. Garden AS, Harris J, Vokes EE, et al. Preliminary results of Radiation Therapy Oncology Group 97-03: A randomized phase II trial of concurrent radiation and chemotherapy for advanced squamous cell carcinomas of the head and neck. J Clin Oncol 2004;22:2856-2864. 7. Taylor S, Murthy A, Vannetzel J, et al. Randomized comparison of neoadjuvant cisplatin and fluorouracil infusion followed by radiation versus concomitant treatment in advanced head and neck cancer. J Clin Oncol 1994;12:385-395. 8. Suntharalingam M, Haas ML, Conley BA, et al. The use of carboplatin and paclitaxel with daily radiotherapy in patients with locally advanced squamous cell carcinomas of the head and neck. Int J Radiat Oncol Biol Phys 2000;47:49-56. 9. Beckmann GK, Hoppe F, Pfreundner L, et al. Hyperfractionated accelerated radiotherapy in combination with weekly cisplatin for locally advanced head and neck cancer. Head Neck 2005;27:36-43.
Medina JA, Rueda A, de Pasos AS, et al. A phase II study of concomitant boost radiation plus concurrent weekly cisplatin 10. 癌症診療指引151 for locally advanced unresectable head and neck carcinomas. Radiother Oncol 2006;79:34-38 11. Cooper JS, Pajak TF, Forastiere AA, et al. Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. N Engl J Med 2004;350:1937-1944 12. Bernier J, Domenge C, Ozsahin M, et al. Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. N Engl J Med 2004;350:1945-1952 13. Bernier J, Cooper JS, Pajak TF, et al. Defining risk levels in locally advanced head and neck cancers: A comparative analysis of concurrent postoperative radiation plus chemotherapy trials of the EORTC (#22931) and radiotherapyog (# 9501). Head Neck 2005;27:843-850. 14. Bachaud JM, Cohen-Jonathan E, Alzieu C, et al. Combined postoperative radiotherapy and weekly cisplatin infusion for locally advanced head and neck carcinoma: final report of a randomized trial. Int J Radiat Oncol Biol Phys 1996 Dec 1;36:999-1004. 15. Cooper JS, Zhang Q, Pajak TF, et al. Long-term follow-up of the radiotherapyog 9501/intergroup phase III trial: postoperative concurrent radiation therapy and chemotherapy in high-risk squamous cell carcinoma of the head and neck. Int J Radiat Oncol Biol Phys 2012;84:1198-1205. 16. Jeremic B, Milicic B, Dagovic A, et al. Radiation Therapy With or Without Concurrent Low-Dose Daily Chemotherapy in Locally Advanced, Nonmetastatic Squamous Cell Carcinoma of the Head and Neck. J Clin Oncol, 2004, 22:3540-3548 17. RTOG 0522: a randomized phase III trial of concurrent accelerated radiation and cisplatin versus concurrent accelerated radiation, cisplatin, and cetuximab [followed by surgery for selected patients] for Stage III and IV head and neck carcinomas. Clin Adv Hematol Oncol 2007;5: 79-81 18. Gibson MK, Li Y, Murphy B, et al. Randomized phase III evaluation of cisplatin plus fluorouracil versus cisplatin plus paclitaxel in advanced head and neck cancer (E1395): an intergroup trial of the Eastern Cooperative Oncology Group. J Clin Oncol 2005;23:3562-3567 19. Soo KC, Tan EH, Wee J, et al.surgery and adjuvant radiotherapy vs concurrent chemoradiotherapy in stage III/IV nonmetastatic squamous cell head and neck cancer: a randomised comparison. Br J Cancer. 2005;93:279-286
Harari PM, Harris J, Kies MS, et al. Postoperative chemoradiotherapy and cetuximab for high-risk squamous cell 20. 癌症診療指引152 carcinoma of the head and neck: Radiation Therapy Oncology Group radiotherapyog-0234. J Clin Oncol. 2014;32:2486-2495 21. Fietkau R, Lautenschläger C, Sauer R, et al. Postoperative concurrent radio-chemotherapy versus radiotherapy in high-risk SCCA of the head and neck: Results of the German phase III trial ARO 96 32006 ASCO Annual Meeting Proceedings (Post-Meeting Edition)24,(18S) 2006: 5507 22. Vermorken JB, Remenar E, van Herpen C, et al; EORTC 24971/TAX 323 Study Group. Cisplatin, fluorouracil, and docetaxel in unresectable head and neck cancer. NEngl J Med 2007;357(17):1695-1704. 23. 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):1705-1715 24. 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;101:498-506 25. Hitt R, López-Pousa A, Martínez-Trufero J, et al. Phase III study comparing cisplatin plus fluorouracil to paclitaxel, cisplatin, and fluorouracil induction chemotherapy followed by chemoradiotherapy in locally advanced head and neck cancer. J Clin Oncol 2005;23:8636-8645. 26. Paccagnella A, Orlando A, Marchiori C, et al. Phase III trial of initial chemotherapy in stage III or IV head and neck cancers: a study by the Gruppo di Studio sui Tumori della Testa e del Collo. J Natl Cancer Inst. 1994;86:265-272 27. Chitapanarux I, Lorvidhaya V, Kamnerdsupaphon P, et al. Chemoradiation comparing cisplatin versus carboplatin in locally advanced nasopharyngeal cancer: Randomised, non-inferiority, open trial. Eur J Cancer 2007;43:1399-1406 28. Haddad R, O'Neill A, Rabinowits G, et al. Induction chemotherapy followed by concurrent chemoradiotherapy (sequential chemoradiotherapy) versus concurrent chemoradiotherapy alone in locally advanced head and neck cancer (PARADIGM): a randomised phase 3 trial. Lancet Oncol. 2013;14:257-4264 29. Lefebvre JL, Pointreau Y, Rolland F, et al. Induction chemotherapy followed by either chemoradiotherapy or bioradiotherapy for larynx preservation: the TREMPLIN randomized phase II study. J Clin Oncol 2013;31:853-859.
minimally toxic outpatient neoadjuvant chemotherapy for locally advanced squamous cell carcinoma of the head and neck. Cancer 2002; 94 (11): 2982-2995. 31. Wang HM, Hsu CL, Hsieh CH, et al. Concurrent chemoradiotherapy using cisplatin, tegafur, and leucovorin for advanced squamous cell carcinoma of the hypopharynx and oropharynx. Biomed J 2014;37(3):133-40. Hung-Ming Wang, Cheng-Su Wang, Jen-Shi Chen, et al. Cisplatin, tegafur, and leucovorin: A moderately effective and 30. 癌症診療指引153
Unresectable, or Metastatic (incurable) Recurrent, 癌症診療指引154 Combination therapy mg/m 2 Cetuximab 400* 250 1 QW 1 Cisplatin 60-100 1 Q3W Max 6 5-FU 600-1000 1-4 Q3W Max 6 *1 st dose 400 mg/m 2 then followed by 250 mg/m 2 mg/m 2 Cetuximab 400* 250 1 QW 1 Carboplatin 5 AUC 1 Q3W Max 6 5-FU 600-1000 1-4 Q3W Max 6 *1 st dose 400 mg/m 2 then followed by 250 mg/m 2 mg/m 2 Docetaxel 65 1 Q3W 2 Carboplatin 6 AUC 1 Q3W mg/m 2 Paclitaxel 175 1 Q3W 3 Cisplatin 75 1 Q3W mg/m 2 Paclitaxel 175 1 Q3W 3 Carboplatin 6 AUC 1 Q3W
mg/m2 癌症診療指引155 Cetuximab 200* 125 1 QW 4 Cisplatin 100 1 Q4W 2-6 *1 st dose 200 mg/m 2 then followed by 125 mg/m 2 mg/m 2 Cisplatin 60-100 1 Q3W 3, 5 5-FU 600-1000 1-4 Q3W mg/m 2 Cetuximab 400 250 500* 1 QW QW Q2W* 6 Docetaxel 75 1 Q3W 4 Cisplatin 75 1 Q3W 4 *1 st dose 400 mg/m 2 and 2 nd dose 250 mg/m 2 QW then followed by 500 mg/m 2 Q2W mg/m 2 Cetuximab 400 250 500* 1 QW QW Q2W* 21 Docetaxel 75 1 Q3W 4 Carboplatin 5 AUC 1 Q3W 4 *1 st dose 400 mg/m 2 and 2 nd dose 250 mg/m 2 QW then followed by 500 mg/m 2 Q2W
mg/m2 癌症診療指引156 Paclitaxel 175 1 Q3W 2 22, 23 Cisplatin 75 1 Q3W 2 Followed by Cetuximab 400* 250 1 QW Cisplatin 75 1 Q3W 4 *1 st dose 400 mg/m 2 then followed by 250 mg/m 2 mg/m 2 Paclitaxel 175 1 Q3W 2 22, 23 Carboplatin 5-6 AUC 1 Q3W 2 Followed by Cetuximab 400* 250 1 QW Carboplatin 5 AUC 1 Q3W 4 Single agents *1 st dose 400 mg/m 2 then followed by 250 mg/m 2 mg/m 2 Cisplatin 100 1 Q3-4W 7, 8 mg/m 2 Paclitaxel 80 1 QW 6 9
mg/m2 癌症診療指引157 Docetaxel 100 1 Q3W 10 mg/m 2 5-FU 1000 1 Q3W 8 mg/m 2 Methotrexate 40 1 QW 11, 12 mg/m 2 Cetuximab 400* 250 1 QW Min 7 13 *1 st dose 400 mg/m 2 then followed by 250 mg/m 2 mg/m 2 Capecitabine 1250 PO BID 1-14 Q3W Min 2 14 mg/m 2 Afatinib 40 mg* PO QDAC QW Min 4 17 *20-50mg mg/m 2 Pembrolizumab 2 mg/kg 1 Q2W 18
mg/m2 癌症診療指引158 Pembrolizumab 200 mg 1 Q3W 19 mg/m 2 Nivolumab 3 mg/kg 1 Q2W 20 1. Vermorken JB, Mesia R, Rivera F, et al. Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med 2008;359:1116-1127. 2. Samlowski WE, Moon J, Kuebler JP, et al. Evaluation of the combination of docetaxel/carboplatin in patients with metastatic or recurrent squamous cell carcinoma of the head and neck (SCCHN): a Southwest Oncology Group Phase II study. Cancer Invest 2007;25:182-188. 3. Gibson MK, Li Y, Murphy B, et al. Randomized phase III evaluation of cisplatin plus fluorouracil versus cisplatin plus paclitaxel in advanced head and neck cancer (E1395): An Intergroup Trial of the Eastern Cooperative Oncology Group. J Clin Oncol 2005;23:3562-3567. 4. Burtness B, Goldwasser MA, Flood W, et al. Phase III randomized trial of cisplatin plus placebo versus cisplatin plus cetuximab in metastatic/recurrent head and neck cancer: An Eastern Cooperative Oncology Group Study. J Clin Oncol 2005;23:8646-8654. 5. Forastiere AA, Metch B, Schuller DE, et al. Randomized comparison of cisplatin plus flurouracil 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;10:1245-1251. 6. Guigay J, Fayette J, Dillies A-F, et al. Cetuximab, docetaxel, and cisplatin (TPEx) as first-line treatment in patients with recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN): Final results of phase II trial
2008-03 [abstract]. J Clin Oncol 2012;30(Suppl 15):Abstract 5505. GORTEC 癌症診療指引159 7. Burthese B, Goldwasser MA, Flood W, et al. Phase III Randomized Trial of Cisplatin Plus Placebo Compared With Cisplatin Plus Cetuximab in Metastatic/Recurrent Head and Neck Cancer: An Eastern Cooperative Oncology Group Study. J Clin Oncol 2005;23:8646-8654. 8. Jacobs C, Lyman G, Velez-Garcia E, et al. A phase III randomized study comparing cisplatin and fluorouracil as single agents and in combination for advanced squamous cell carcinoma of the head and neck. J Clin Oncol 1992;10:257-263. 9. Grau JJ, Caballero M, Verger E, et al. Weekly paclitaxel for platin-resistant stage IV head and neck cancer patients. Acta OtoLaryngol 2009;129:1294-1299. 10. Catimel1 G, Verweij J, Mattijssen V, et al. Docetaxel (Taxotere): An active drug for the treatment of patients with advanced squamous cell carcinoma of the head and neck. Ann Oncol 1994;5:533-537. 11. 11. Stewart JS, Cohen EE, Licitra L, et al. Phase III study of gefitinib compared with intravenous methotrexate for recurrent squamous cell carcinoma of the head and neck [corrected]. J Clin Oncol 2009;27:1864-1871 12. 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 Aug;10(8):1245-51. 13. 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 Jun 1;25(16):2171-7. 14. Martinez-Trufero J, Isla D, Adansa JC, et al. Phase II study of capecitabine as palliative treatment for patients with recurrent and metastatic squamous head and neck cancer after previous platinum-based treatment. Br J Cancer 2010;102:1687-1691. 15. Degardin M, Oliveira J, Geoffrois L, An EORTC-ECSG phase II study of vinorelbine in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck. Ann Oncol 1998;9: 1103-1107. 16. Saxman S, Mann B, Canfield V, et al. A Phase II Trial of Vinorelbine in Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck. Am J Clin Oncol 1998;21:398-400. 17. Machiels JP, Haddad RI, Fayette J, et al. Afatinib versus methotrexate as second-line treatment in patients with recurrent
metastatic squamous-cell carcinoma of the head and neck progressing on after platinum-based therapy (LUX-Head or 癌症診療指引160 & Neck 1): an open-label, randomised phase 3 trial. Lancet Oncol 2015;16:583-594. 18. Seiwent TY, Burtness B, Mehra R, et al. Safety and clinical activity of pembrolizumab for treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-012): an open-label, multicentre, phase 1b trial. Lancet 2016;17:956-965. 19. Chow LQ, Haddad R, Gupta S, et al. Antitumor Activity of Pembrolizumab in Biomarker-Unselected Patients With Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma: Results From the Phase Ib KEYNOTE-012 Expansion Cohort. J Clin Oncol 2016. 20. Ferris R, Blumenschein G, Fayette J, et al. further evaluations of nivolumab versus investigator's choice chemotherapy for recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck: CheckMate-141. Oral presentation at The American Society of Clinical Oncology (ASCO) 2016 Annual Meeting; June 3-7, 2016; Chicago, Illinois. 21. Joel Guigay UK, Ricard Mesia, Nadejda Vintonenko, Jean Bourhis, Anne Auperin. TPExtreme randomized trial: TPEx versus Extreme regimen in 1st line recurrent/metastatic head and neck squamous cell carcinoma. Journal of Clinical Oncology 2015. 22. Price KA, Cohen EE. Current treatment options for metastatic head and neck cancer. Curr Treat Options Oncol 2012;13:35-46. 23. Herbst RS, Arquette M, Shin DM, et al. Phase II multicenter study of the epidermal growth factor receptor antibody cetuximab and cisplatin for recurrent and refractory squamous cell carcinoma of the head and neck. J Clin Oncol 2005;23:5578-5587.
Nasopharynx 癌症診療指引161 Chemoradiation followed by adjuvant chemotherapy mg/m 2 Cisplatin 60-100 1 Q3W 3 with RT 1 Followed by Cisplatin 60-100 1 Q4W 3 after RT 5-FU 600-1000 1-4 Q4W 3 after RT mg/m 2 Carboplatin 6 AUC 1 Q3W 3-5 with RT 2 Followed by Carboplatin 5 AUC 1 Q3W 2 after RT 5-FU 1000* 1-4 Q3W 2 after RT *Continuous infusion for 24 h mg/m 2 Cisplatin 20-40 1 QW 7 3 mg/m 2 Cisplatin 50 1 Q2W 6 13 UFUR 800 mg* PO 1-14 Q2W Leucovorin 60 mg PO 1-14 Q2W *Or 300 mg/m 2
(Category 3)/Sequential chemotherapy Induction 癌症診療指引162 mg/m 2 Docetaxel 60-70 1 Q3W 3 4 Cisplatin 60-75 1 Q3W 3 5-FU 750-1000* 1-4 Q3W 3 Followed by Cisplatin 100 1 Q3W With RT mg/m 2 Docetaxel 60-75 1 Q3W 2 5 Cisplatin 60-75 1 Q3W 2 Followed by Cisplatin 40 1 QW With RT mg/m 2 Cisplatin 60-100 1 Q3W 3 6 5-FU 600-1000 1-4 Q3W 3 *Continuous infusion for 24 h mg/m 2 Epirubicin 75 1 Q3W 3 7 Paclitaxel 175 1 Q3W 3 Cisplatin 60-75 2 Q3W 3 Followed by Paclitaxel 60 1 QW During RT
mg/m2 癌症診療指引163 Cisplatin 40 1 QW 7 during RT 8 mg/m 2 Epirubicin 60-75 1 Q4W 3 9 Mitomycin 10 1 Q4W Cycle 1, 3 only Cisplatin 60-100 1 Q4W 3 Adjuvant CT (post RT or CCRT completion on day 29) (category 2B) mg/m 2 Cisplatin 80 1 Q4W 3 10 5-FU 1000 1-4 Q4W 3 Following induction, agents to be used with concurrent chemoradiation typically include weekly cisplatin or carboplatin mg/m 2 Cisplatin 40 1 QW 7 11 mg/m 2 Carboplatin 1.5-2 AUC 1 QW 6 12 1. Al-Sarraf M, LeBlanc M, Giri PG, Fu KK, et al. Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: phase III randomized Intergroup study 0099. J Clin Oncol. 1998 ;16:1310-1317. 2. Dechaphunkul T, Pruegsanusak K, Sangthawan D, et al. Concurrent chemoradiotherapy with carboplatin followed by
and 5-fluorouracil locally advanced nasopharyngeal carcinoma. Head Neck Oncol. 2011;3:30. carboplatin 癌症診療指引164 3. Chen L, Hu CS, Chen XZ, et al. Concurrent chemoradiotherapy plus adjuvant chemotherapy versus concurrent chemoradiotherapy alone in patients with locoregionally advanced nasopharyngeal carcinoma: a phase 3 multicentre randomised controlled trial. Lancet Oncol. 2012;13:163-171. 4. Bae WK, Hwang JE, Shim HJ, et al. Phase II study of docetaxel, cisplatin, and 5-FU induction chemotherapy followed by chemoradiotherapy in locoregionally advanced nasopharyngeal cancer. Cancer Chemother Pharmacol. 2010;65:589-595. 5. Hui EP, Ma BB, Leung SF, et al, Randomized phase II trial of concurrent cisplatin-radiotherapy with or without neoadjuvant docetaxel and cisplatin in advanced nasopharyngeal carcinoma. J Clin Oncol. 2009;27:242-249. 6. 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):1705-1715. 7. Fountzilas G, Tolis C, Kalogera-Fountzila A, et al. Induction chemotherapy with cisplatin, epirubicin, and paclitaxel (CEP), followed by concomitant radiotherapy and weekly paclitaxel for the management of locally advanced nasopharyngeal carcinoma. 8. A Hellenic Cooperative Oncology Group phase II study. Strahlenther Onkol. 2005;181:223-230. 9. 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. 2001;19:4305-4313. 10. Muhyi al-sarraf, Martine Leblanc, et al. Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: phase III randomized Intergroup study 0099. J Clin Oncol 1998; 16: 1310-1317. 11. 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 Apr 6;97(7):536-539. 12. Chitapanarux I, Lorvidhaya V, Kamnerdsupaphon P, Chemoradiation comparing cisplatin versus carboplatin in locally advanced nasopharyngeal cancer: randomised, non-inferiority, open trial. Eur J Cancer. 2007;43:1399-1406. 13. Concurrent chemoradiotherapy using biweekly cisplatin/tegafur plus uracil/leucovorin in stage III nasopharyngeal carcinoma. J Clin Oncol. 2005 23(16): 5510
Unresectable, or Metastatic (incurable) Recurrent, 癌症診療指引165 Combination therapy mg/m 2 Docetaxel 65 1 Q3W 1 Carboplatin 6 AUC 1 Q3W mg/m 2 Cisplatin 75 1 Q3W Min 6 2 Paclitaxel 175 1 Q3W Min 6 mg/m 2 Carboplatin 6 AUC 1 Q3W Min 6 2 Paclitaxel 175 1 Q3W Min 6 mg/m 2 Cisplatin 6 AUC 1 Q3W Min 6 2 Docetaxel 65 1 Q3W Min 6 mg/m 2 Cisplatin 60-100 1 Q3W Min 6 2, 3 5-FU 600-1000 1-4 Q3W Min 6
mg/m2 癌症診療指引166 Carboplatin 5 AUC 1 Q3W Max 8 4 Cetuximab 400* 250 1 QW *1 st dose 400 mg/m 2 then followed by 250 mg/m 2 mg/m 2 Cisplatin 20-30* 1-3 Q3W 5 Gemcitabine 1000 1, 8 Q3W Single agents *80 mg/m 2 in divided doses on 3 days mg/m 2 Cisplatin 100 1 Q3-4W Min 4 6, 7 mg/m 2 Carboplatin 6 AUC 1 Q3W 14 mg/m 2 Paclitaxel 80 1 QW 6 8 mg/m 2 Docetaxel 100 1 Q3W 9
mg/m2 癌症診療指引167 5-FU 1000 1 Q3W 7 mg/m 2 Methotrexate 40 1 QW 10, 11 mg/m 2 Gemcitabine 1000 1, 8, 15 Q4W 12 mg/m 2 Capecitabine 1250 PO BID 1-14 Q3W Min 2 13 1. Samlowski WE, Moon J, Kuebler JP, et al. Evaluation of the combination of docetaxel/carboplatin in patients with metastatic or recurrent squamous cell carcinoma of the head and neck (SCCHN): a Southwest Oncology Group Phase II study. Cancer Invest 2007;25:182-188. 2. Gibson MK, Li Y, Murphy B, et al. Randomized phase III evaluation of cisplatin plus fluorouracil versus cisplatin plus paclitaxel in advanced head and neck cancer (E1395): An Intergroup Trial of the Eastern Cooperative Oncology Group. J Clin Oncol 2005;23:3562-3567. 3. Forastiere AA, Metch B, Schuller DE, et al. Randomized comparison of cisplatin plus flurouracil 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;10:1245-1251. 4. Chan AT, Hsu MM, Goh BC, et al. Multicenter, phase II study of cetuximab in combination with carboplatin in patients with recurrent or metastatic nasopharyngeal carcinoma. J Clin Oncol 2005;23:3568-3576. 5. Jin Y, Cai XY, Shi YX, et al. Comparison of five cisplatin-based regimens frequently used as the first-line protocols in
nasopharyngeal carcinoma. J Cancer Res Clin Oncol 2012 Oct;138(10):1717-25. metastatic 癌症診療指引168 6. Burthese B, Goldwasser MA, Flood W, et al. Phase III Randomized Trial of Cisplatin Plus Placebo Compared With Cisplatin Plus Cetuximab in Metastatic/Recurrent Head and Neck Cancer: An Eastern Cooperative Oncology Group Study. J Clin Oncol 2005;23:8646-8654. 7. Jacobs C, Lyman G, Velez-Garcia E, et al. A phase III randomized study comparing cisplatin and fluorouracil as single agents and in combination for advanced squamous cell carcinoma of the head and neck. J Clin Oncol 1992;10:257-263. 8. Grau JJ, Caballero M, Verger E, et al. Weekly paclitaxel for platin-resistant stage IV head and neck cancer patients. Acta OtoLaryngol 2009;129:1294-1299. 9. Catimel1 G, Verweij J, Mattijssen V, et al. Docetaxel (Taxotere): An active drug for the treatment of patients with advanced squamous cell carcinoma of the head and neck. Ann Oncol 1994;5:533-537. 10. Stewart JS, Cohen EE, Licitra L, et al. Phase III study of gefitinib compared with intravenous methotrexate for recurrent squamous cell carcinoma of the head and neck [corrected]. J Clin Oncol 2009;27:1864-1871 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 Aug;10(8):1245-51. 12. Zhang L, Zhang Y, Huang PY, et al. 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;61:33-8. Epub 2007 Mar 20. 13. Martinez-Trufero J, Isla D, Adansa JC, et al. Phase II study of capecitabine as palliative treatment for patients with recurrent and metastatic squamous head and neck cancer after previous platinum-based treatment. Br J Cancer 2010;102:1687-1691. 14. Al-Sarraf M, Metch B, Kish J, et al. Platinum analogs in recurrent and advanced head and neck cancer: a Southwest Oncology Group and Wayne State University Study. Cancer Treat Rep 1987;71:732-736.