耳鼻咽喉科・頭頸部外科86巻10号

2014年09月発行

特集 咽頭癌・頸部食道癌の治療戦略Update ≪放射線療法と薬物療法≫

分子標的薬時代の咽頭癌に対する薬物療法

著者： 田口享秀¹ 折舘伸彦¹

所属機関： ¹横浜市立大学医学部耳鼻咽喉科・頭頸部外科

ページ範囲：P.828 - P.833

POINT

●現在，頭頸部癌においてセツキシマブ（cetuximab）が唯一の分子標的薬として進行症例を対象に承認されている。

●一次治療として，放射線治療とセツキシマブの同時併用は，シスプラチンを含む従来の化学放射線療法とともに治療選択肢の1つに挙げられる。

●再発あるいは遠隔転移で根治治療ができない頭頸部扁平上皮癌症例に対して，白金製剤，フルオロウラシル，セツキシマブの併用は有用な治療法と考えられる。

●セツキシマブの併用法として，導入化学療法後の放射線治療への併用，導入化学療法への併用，術後補助療法としての放射線治療への併用なども検討されている。

参考文献

1）Induction chemotherapy plus radiation compared with surgery plus radiation in patients with advanced laryngeal cancer. The Department of Veterans Affairs Laryngeal Cancer Study Group. N Engl J Med 324：1685-1690, 1991

2）Pignon JP, et al：Chemotherapy added to locoregional treatment for head and neck squamous-cell carcinoma：three meta-analyses of updated individual data. MACH-NC Collaborative Group. Meta-Analysis of Chemotherapy on Head and Neck Cancer. Lancet 355：949-955, 2000

3）Forastiere AA, et al：Long-term results of RTOG 91-11：a comparison of three nonsurgical treatment strategies to preserve the larynx in patients with locally advanced larynx cancer. J Clin Oncol 31：845-852, 2013

4）Vermorken JB, et al：Cisplatin, fluorouracil, and docetaxel in unresectable head and neck cancer. N Engl J Med 357：1695-1704, 2007

5）Posner MR, et al：Cisplatin and fluorouracil alone or with docetaxel in head and neck cancer. N Engl J Med 357：1705-1715, 2007

6）Pointreau Y, et al：Randomized trial of induction chemotherapy with cisplatin and 5-fluorouracil with or without docetaxel for larynx preservation. J Natl Cancer Inst 101：498-506, 2009

7）Adelstein DJ, 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 21：92-98, 2003

8）Denis F, et al：Final results of the 94-01 French Head and Neck Oncology and Radiotherapy Group randomized trial comparing radiotherapy alone with concomitant radiochemotherapy in advanced-stage oropharynx carcinoma. J Clin Oncol 22：69-76, 2004

9）Lefebvre JL, et al：Larynx preservation in pyriform sinus cancer：preliminary results of a European Organization for Research and Treatment of Cancer phase Ⅲ trial. EORTC Head and Neck Cancer Cooperative Group. J Natl Cancer Inst 88：890-899, 1996

10）Lefebvre JL, et al：Laryngeal preservation with induction chemotherapy for hypopharyngeal squamous cell carcinoma：10-year results of EORTC trial 24891. Ann Oncol 23：2708-2714, 2012

11）Prades JM, et al：Randomized phase Ⅲ trial comparing induction chemotherapy followed by radiotherapy to concomitant chemoradiotherapy for laryngeal preservation in T3M0 pyriform sinus carcinoma. Acta Otolaryngol 130：150-155, 2010

12）Bensadoun RJ, et al：French multicenter phase Ⅲ randomized study testing concurrent twice-a-day radiotherapy and cisplatin/5-fluorouracil chemotherapy（BiRCF）in unresectable pharyngeal carcinoma：Results at 2 years（FNCLCC-GORTEC）. Int J Radiat Oncol Biol Phys 64：983-994, 2006

13）National Comprehensive Cancer Network（NCCN）clinical practice guidelines in oncology：head and neck cancers. 2014 version 2

14）Beauvillain C, et al：Final results of a randomized trial comparing chemotherapy plus radiotherapy with chemotherapy plus surgery plus radiotherapy in locally advanced resectable hypopharyngeal carcinomas. Laryngoscope 107：648-653, 1997

15）Haddad R, 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 14：257-264, 2013

16）Bernier J, et al：Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. N Engl J Med 350：1945-1952, 2004

17）Bernier J, 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 27：843-850, 2005

18）Taguchi T, et al：Adjuvant chemotherapy with S-1 after curative treatment in patients with head and neck cancer（ACTS-HNC）. J Clin Oncol 31：abstr 6004, 2013

19）Katori H, et al：Phase Ⅰ trial of concurrent chemoradiotherapy with docetaxel, cisplatin and 5-fluorouracil（TPF）in patients with locally advanced squamous cell carcinoma of the head and neck（SCCHN）. Br J Cancer 90：348-352, 2004

20）Tsukuda M, et al：Randomized controlled phase Ⅱ comparison study of concurrent chemoradiotherapy with docetaxel, cisplatin, and 5-fluorouracil versus CCRT with cisplatin, 5-fluorouracil, methotrexate and leucovorin in patients with locally advanced squamous cell carcinoma of the head and neck. Cancer Chemother Pharmacol 66：729-736, 2010

21）Shiga K, et al：Concomitant chemoradiotherapy as a standard treatment for squamous cell carcinoma of the temporal bone. Skull Base 21：153-158, 2011

22）Komatsu M, et al：Concurrent chemoradiotherapy with docetaxel, cisplatin and 5-fluorouracil（TPF）in patients with locally advanced squamous cell carcinoma of the head and neck. Jpn J Clin Oncol 44：416-421, 2014

23）Taguchi T, et al：Treatment results and prognostic factors for advanced squamous cell carcinoma of the hypopharynx treated with concurrent chemoradiotherapy. Cancer Chemother Pharmacol 73：1147-1154, 2014

24）田口享秀，他：下咽頭扁平上皮癌に対する化学放射線療法（全身化学療法）の適応と限界．耳鼻臨床107：85-92，2014

25）Bonner JA, et al：Radiotherapy plus セツキシマブ for squamous-cell carcinoma of the head and neck. N Engl J Med 354：567-578, 2006

26）Bonner JA, 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 11：21-28, 2010

27）Barni S, et al：Cisplatin versus cetuximab plus concomitant radiotherapy in locally advanced head and neck cancer：A meta-analysis of published trials. J Clin Oncol 32：abstr 6014, 2014

28）久保田　彰：海外のphase Ⅲ試験から頭頸部悪性腫瘍に対する分子標的薬の意義を考える．耳鼻58：S16-S26，2012

29）田原　信：初回治療でここまで治る—適応と成績．分子標的薬の可能性．JOHNS 29：1005-1012，2013

30）Ang KK, et al：A randomized phase Ⅲ trial（RTOG 0522）of concurrent accelerated radiation plus cisplatin with or without cetuximab for stage Ⅲ-Ⅳ head and neck squamous cell carcinomas. J Clin Oncol 29：abstr 5500, 2011

31）Lefebvre JL, et al：Induction chemotherapy followed by either chemoradiotherapy or bioradiotherapy for larynx preservation：the TREMPLIN randomized phase Ⅱ study. J Clin Oncol 31：853-859, 2013

32）Harari PM, et al：Postoperative Chemoradiotherapy and Cetuximab for High-Risk Squamous Cell Carcinoma of the Head and Neck：Radiation Therapy Oncology Group RTOG-0234. J Clin Oncol, 2014

33）Vermorken JB, et al：Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med 359：1116-1127, 2008

34）Hitt R, et al：Phase Ⅱ study of the combination of cetuximab and weekly paclitaxel in the first-line treatment of patients with recurrent and/or metastatic squamous cell carcinoma of head and neck. Ann Oncol 23：1016-1022, 2012

35）Guigay J, 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 2008-03. J Clin Oncol 30：abstr 5505, 2012

36）Al-Sarraf M, et al：Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer：phase Ⅲ randomized Intergroup study 0099. J Clin Oncol 16：1310-1317, 1998

37）Chan AT, et al：Overall survival after concurrent cisplatin-radiotherapy compared with radiotherapy alone in locoregionally advanced nasopharyngeal carcinoma. J Natl Cancer Inst 97：536-539, 2005

38）Lin JC, et al：Phase Ⅲ study of concurrent chemoradiotherapy versus radiotherapy alone for advanced nasopharyngeal carcinoma：positive effect on overall and progression-free survival. J Clin Oncol 21：631-637, 2003

39）Chen L, 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 13：163-171, 2012