癌症診療指引274 Squamous Cell Cancers Lip, Oral Cavity, Oropharynx, Hypopharynx, Glottic Larynx, Supraglottic Larynx, Ethmoid Sinus, Maxillary Sinus, Occult

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1 癌症診療指引274 Squamous Cell Cancers Lip, Oral Cavity, Oropharynx, Hypopharynx, Glottic Larynx, Supraglottic Larynx, Ethmoid Sinus, Maxillary Sinus, Occult Primary Primary systemic therapy + concurrent radiotherapy High-dose cisplatin (preferred) (category 1) Cisplatin 75~100 1 Q3W 1,2 Cetuximab (category 1) Cetuximab QW 3 Cetuximab QW Carboplatin/infusional 5-FU (category 1) Carboplatin 70 1~4 Q3W 4 Fluorouracil 600 1~4 Q3W Carboplatin 70 1~5 Q4W 5 Fluorouracil 600 1~5 Q4W

2 5-FU/Hydroxyurea 癌症診療指引275 Hydroxyurea 1g PO BID 11 doses Q2W 6 Fluorouracil 800 1~5 Q2W Cisplatin/Paclitaxel Paclitaxel 30 1 QW 6 Cisplatin 20 2 QW Paclitaxel Q3W 8 Cisplatin 75 1 Q3W Cisplatin/infusional 5-FU Cisplatin Q3W 7 Fluorouracil ~5 Q3W Cisplatin 60 1 Q2W 7 Fluorouracil 800 1~5 Q2W

3 /m2 癌症診療指引276 Cisplatin 20 1~4 Q4W 19 Fluorouracil ~4 Q4W Cisplatin Q3W 18 Fluorouracil ~4 Q3W Carboplatin/paclitaxel (category 2B) Carboplatin QW 8 Paclitaxel QW Weekly cisplatin (category 2B) Cisplatin QW 9 Cisplatin 40 1 QW 10

4 daily Carboplatin 癌症診療指引277 Carboplatin 25 1~5 QW 16 Definitive CCRT + Cetuximab Cisplatin , 22, 43 Q3W 17 Cetuximab QW Cetuximab QW Cisplatin/Tegafur/Leucovorin Cisplatin 50 1 Q2W 31 UFUR 800 mg PO 1-14 Q2W Leucovorin 60 mg PO 1-14 Q2W Postoperative Chemoradiation Cisplatin(category 1 for high risk) Cisplatin , 22, 43 Q3W 11,12, 13,15 Cisplatin QW 20

5 compare to Intergroup 9501) (RTOG0234 癌症診療指引278 Cetuximab 400 for once at 5-9 days QW 20 Cetuximab QW Cisplatin 30 1 QW Cetuximab 400 for once at 5-9 days QW 20 Cetuximab QW Docetaxel 15 1 QW Cisplatin/infusional 5-FU Cisplatin 20 1~5, 29~33 Q4W 21 Fluorouracil 600 1~5, 29~33 Q4W

6 Oral Cavity, Oropharynx, Hypopharynx, Glottic Larynx, Supraglottic Larynx, Ethmoid Sinus, Maxillary Lip, 癌症診療指引279 Sinus, Occult Primary Induction/Sequential chemotherapy Docetaxel/cisplatin/5-FU (category 1 if induction is chosen) Docetaxel Q3W 22,24 Cisplatin Q3W Fluorouracil ~5 Q3W Docetaxel Q3W 23 Cisplatin Q3W Fluorouracil ~4 Q3W Paclitaxel/cisplatin/infusional 5-FU Paclitaxel Q3W 25 Cisplatin Q3W Fluorouracil 500 2~6 Q3W Cisplatin + 5-FU Cisplatin Q3W 26 Fluorouracil /day 3~5 Q3W

7 induction, agents to be used with concurrent chemoradiation typically include weekly carboplatin or cetuximab Following 癌症診療指引280 Carboplatin 100 1, 8, 15, 22, 29, 36 QW 27 Carboplatin 1.5 AUC 1 QW 28 Cetuximab QW 29 Cetuximab QW Cisplatin/Tegafur/Leucovorin Cisplatin 50 1 Q2W 30 UFUR 800 mg PO 1-14 Q2W Leucovorin 60 mg PO 1-14 Q2W 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: Adelstein DJ, Li Y, Adams GL, et al. An intergroup phase III comparison of standard radiation therapy and two schedules

8 concurrent chemoradiotherapy in patients with unresectable squamous cell head and neck cancer. J Clin Oncol of 癌症診療指引 ;21(1): 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: Denis F, Garaud P, Bardet E, et al. Final results of the 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: 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: 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: 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: 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: 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: Medina JA, Rueda A, de Pasos AS, et al. A phase II study of concomitant boost radiation plus concurrent weekly cisplatin for locally advanced unresectable head and neck carcinomas. Radiother Oncol 2006;79: 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: 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:

9 Bernier J, Cooper JS, Pajak TF, et al. Defining risk levels in locally advanced head and neck cancers: A comparative 13. 癌症診療指引282 analysis of concurrent postoperative radiation plus chemotherapy trials of the EORTC (#22931) and radiotherapyog (# 9501). Head Neck 2005;27: 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: 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: 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: 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: 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: 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: Harari PM, Harris J, Kies MS, et al. Postoperative chemoradiotherapy and cetuximab for high-risk squamous cell carcinoma of the head and neck: Radiation Therapy Oncology Group radiotherapyog J Clin Oncol. 2014;32: Fietkau R, Lautenschläger C, Sauer R, et al. Postoperative concurrent radio-chemotherapy versus radiotherapy in

10 SCCA of the head and neck: Results of the German phase III trial ARO ASCO Annual Meeting high-risk 癌症診療指引283 Proceedings (Post-Meeting Edition)24,(18S) 2006: 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): 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: 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: 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: 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: 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: 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: Hung-Ming Wang, Cheng-Su Wang, Jen-Shi Chen, et al. Cisplatin, tegafur, and leucovorin: A moderately effective and minimally toxic outpatient neoadjuvant chemotherapy for locally advanced squamous cell carcinoma of the head and neck. Cancer 2002; 94 (11):

11 Unresectable, or Metastatic (incurable) Recurrent, 癌症診療指引284 Combination therapy Cisplatin/5-FU/cetuximab (category 1) Cisplatin Q3W max 6 cycles 1 Fluorouracil Q3W Cetuximab QW Cetuximab QW Carboplatin/5-FU/cetuximab (category 1) Carboplatin 5 AUC 1 Q3W max 6 cycles 1 Fluorouracil Q3W Cetuximab QW Cetuximab QW Carboplatin/Docetaxel Docetaxel 65 1 Q3W 2 Carboplatin 6 AUC 1 Q3W

12 Cisplatin/paclitaxel 癌症診療指引285 Cisplatin 75 1 Q3W 3 Paclitaxel Q3W Carboplatin/Paclitaxel Carboplatin 6 AUC 1 Q3W 3 Paclitaxel Q3W Cisplatin/Cetuximab Cisplatin Q4W 4 Cetuximab QW Cetuximab QW Cisplatin/5-FU Cisplatin Q3W 3,5 Fluorouracil Q3W

13 Cisplatin/Docetaxel/Cetuximab 癌症診療指引286 Docetaxel 75 1 Q3W 4 cycles 6 Cisplatin 75 1 Q3W Cetuximab QW Cetuximab QW Cetuximab Q2W Single agents Cispaltin Q3~4W 7, 8 Paclitaxel 80 1 QW 9 Docetaxel Q3W 10 5-FU Q3W 8

14 /m2 癌症診療指引287 MTX 40 1 QW 11, 12 Cetuximab 400 QW 13 Capecitabine 1250 PO BID 1~14 Q3W 2 cycle+ 14 Vinorelbine 30 QW 15, 16 Afatinib 40 mg PO QDAC 17 Pembrolizumab 2~10 mg/kg Q2W 24 month 18 Pembrolizumab 200 mg Q3W 24 month 19 Nivolumab 3 mg/kg Q2W 20

15 癌症診療指引 Vermorken JB, Mesia R, Rivera F, et al. Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med 2008;359: 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: 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: 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: 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: 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 GORTEC [abstract]. J Clin Oncol 2012;30(Suppl 15):Abstract 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: 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: Grau JJ, Caballero M, Verger E, et al. Weekly paclitaxel for platin-resistant stage IV head and neck cancer patients. Acta

16 2009;129: OtoLaryngol 癌症診療指引 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: 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: 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 Aug;10(8): 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 Jun 1;25(16): 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: 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: 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: Machiels JP, Haddad RI, Fayette J, et al. Afatinib versus methotrexate as second-line treatment in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck progressing on or after platinum-based therapy (LUX-Head & Neck 1): an open-label, randomised phase 3 trial. Lancet Oncol 2015;16: 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: 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

17 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. Cohort. J Clin Oncol Expansion 癌症診療指引290

18 Nasopharynx 癌症診療指引291 Chemoradiation followed by adjuvant chemotherapy Cisplatin + RT followed by cisplatin/5-fu Cisplatin , 22, 43 1 Cisplatin Q4W 5-FU Q4W Carboplatin/5-FU (Category 2B) Carboplatin 6 AUC 1 Q3W 2 Carboplatin 5 AUC 1 Q3W 5-FU Q3W Cisplatin + RT without chemotherapy (Category 2B) Cisplatin QW 3

19 + RT Cisplatin/Tegafur/Leucovorin 癌症診療指引292 Cisplatin 50 1 Q2W 13 UFUR 800 mg PO 1-14 Q2W Leucovorin 60 mg PO 1-14 Q2W Induction (Category 3)/Sequential chemotherapy Docetaxel/Cisplatin/5-FU Docetaxel Q3W 4 Cisplatin Q3W 5-FU Q3W Cisplatin Q3W Docetaxel/cisplatin (category 2B) Docetaxel Q3W 5 Cisplatin Q3W Cisplatin 40 1 QW

20 Cisplatin/5-FU 癌症診療指引293 Cisplatin Q3W 6 5-FU Q3W Cisplatin/Epirubicin/Paclitaxel Epirubicin 75 1 Q3W 7 Paclitaxel Q3W Cisplatin Q3W Paclitaxel 60 1 QW Cisplatin 40 1 QW 8 Cisplatin/Epirubicin/Mitomycin Epirubicin Q4W 9 Mitomycin 10 1 Q4W Cisplatin Q4W Paclitaxel 60 1 QW

21 CT (post RT or CCRT completion on day 29) (category 2B) Adjuvant 癌症診療指引294 Cisplatin 80 1 Q4W 10 5-FU Q4W Leucovorin 1-4 Q4W Cisplatin FU Leucovorin 1-4 Following induction, agents to be used with concurrent chemoradiation typically include weekly cisplatin or carboplatin Cisplatin 40 1 QW 11 Carboplatin 100 1, 8, 15, 22, 29, 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 J Clin Oncol ;16: Dechaphunkul T, Pruegsanusak K, Sangthawan D, et al. Concurrent chemoradiotherapy with carboplatin followed by

22 and 5-fluorouracil locally advanced nasopharyngeal carcinoma. Head Neck Oncol. 2011;3:30. carboplatin 癌症診療指引 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: 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: 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: 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): 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: 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: 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: 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 Apr 6;97(7): 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: Concurrent chemoradiotherapy using biweekly cisplatin/tegafur plus uracil/leucovorin in stage III nasopharyngeal carcinoma. J Clin Oncol (16): 5510

23 Unresectable, or Metastatic (incurable) Recurrent, 癌症診療指引296 Combination therapy Carboplatin/Docetaxel Docetaxel 65 1 Q3W 1 Carboplatin 6 AUC 1 Q3W Cisplatin/Paclitaxel Cisplatin 75 1 Q3W 2 Paclitaxel Q3W Carboplatin/Paclitaxel Carboplatin 6 AUC 1 Q3W 2 Paclitaxel Q3W Cisplatin/5-FU Cisplatin Q3W 2,3 Fluorouracil Q3W

24 Carboplatin/Cetuximab 癌症診療指引297 Carboplatin 5 AUC 1 Q3W 4 Cetuximab QW Cetuximab QW Cisplatin/Gemcitabine Cisplatin Q3W 5 Gemcitabine ,8 Q3W Single agents Cispaltin 100 Q3~4W 6,7 Paclitaxel 80 QW 8 Docetaxel 100 Q3W 9 5-FU 1000 Q3W 7

25 /m2 癌症診療指引298 MTX 40 QW 10, 11 Gemcitabine , 8, 15 Q4W 12 Capecitabine 1250 PO 1~14 Q3W 13 Pembrolizumab 2~10 mg/kg Q2W 14 Pembrolizumab 200 mg Q3W 15 Nivolumab 3 mg/kg 1 Q2W 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:

26 Gibson MK, Li Y, Murphy B, et al. Randomized phase III evaluation of cisplatin plus fluorouracil versus cisplatin plus 2. 癌症診療指引299 paclitaxel in advanced head and neck cancer (E1395): An Intergroup Trial of the Eastern Cooperative Oncology Group. J Clin Oncol 2005;23: 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: 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: Jin Y, Cai XY, Shi YX, et al. Comparison of five cisplatin-based regimens frequently used as the first-line protocols in metastatic nasopharyngeal carcinoma. J Cancer Res Clin Oncol 2012 Oct;138(10): 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: 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: Grau JJ, Caballero M, Verger E, et al. Weekly paclitaxel for platin-resistant stage IV head and neck cancer patients. Acta OtoLaryngol 2009;129: 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: 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: 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 Aug;10(8): 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-

27 Epub 2007 Mar 癌症診療指引 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: 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: 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 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.