Chinese expert consensus on diagnosis and treatment of nasopharyngeal carcinoma: evidence from current practice and future perspectives

Figures & data

Box 1: Tumor staging in nasopharyngeal carcinoma

Recommendations T1: Nasopharynx, adjacent soft tissue extension. T2: Bony structure, paranasal sinuses. T3: Intracranial extension, cranial nerve, hypopharynx, orbit, infratemporal fossa (masticatory space).

Box 2: Treatment recommendations in stage II NPC

Recommendations (i) For conventional radical radiotherapy, a dose fraction of 2.0 Gy/fx and a total dose of 66–70 Gy/33–35fx are recommended. For IMRT, a fractioned dose of 2.12–2.25 Gy/fx and a total dose of 66–72 Gy (30–33 times) are recommended. Patients with a significant residual disease after irradiation should be administered local extended-dose irradiation or additional 6 Gy external irradiation or stereotactic radiotherapy or breech-loading intracavitary brachytherapy with an additional 6–10 Gy dose. (ii) Patients with parapharyngeal obvious invasion/enlarged neck lymph nodes or retropharyngeal lymph nodes (diameter ≥2.0 cm) are recommended cisplatin monotherapy 35–40 mg/m^2/week or 80–100 mg/m^2/3 weeks.

Abbreviation: IMRT, intensity-modulated radiotherapy.

Box 3: Treatment recommendations for locally advanced NPC

Recommendations 1.Chemotherapy regimen (specific therapeutic dose) and radiotherapy dose For patients undergoing radical radiotherapy with two dimensional technique, a fractioned dose of 2.0 Gy/fx and a total dose of 66–70 Gy/33–35 fx are recommended. For IMRT, a fractioned dose of 2.12–2.25 Gy/fx and a total dose of 66–72 Gy (30–33 times of fractioned dose) are recommended. Patients with a significant residual disease after radiation therapy should be administered local extended-dose irradiation or an additional external irradiation dose of 6 Gy or stereotactic radiotherapy with an additional dose of 6–10 Gy. Patients without contraindications to chemotherapy are recommended to be prescribed with concurrent chemotherapy, with cisplatin monotherapy 35–40 mg/m^2/week or 80–100 mg/m^2 ETW as the mainstay. 2. Adjuvant chemotherapy recommendations (i) Cisplatin + Fluorouracil (PF regimen):^Citation2,Citation34^–^Citation36,Citation45 5-fluorouracil (5-FU) 1000 mg/m^2/day for 4 days [96 hr continuous intravenous (IV) infusion] or 5-FU 800 mg/m^2/day IV infusion for 5 days [120 hrs IV infusion]; Cisplatin (DDP) 80 mg/m^2 IV on day 1 or DDP 20 mg/m^2/day IV infusion on days 1–4; repeat the cycle every 28 days for 2–4 courses. (ii) Fluorouracil + Carboplatin (FC regimen)^Citation:38 5-FU 1000 mg/m^2, 96 hr continuous IV infusion; carboplatin AUC 5 IV on day 1; repeat the cycle every 21 days for 2–4 courses, 3. Induction chemotherapy (neoadjuvant chemotherapy) recommendations (i) Docetaxel, cisplatin, fluorouracil (TPF regimen): Docetaxel 70 mg/m^2 IV on day 1; DDP 75 mg/m^2 IV on day 1; 5-FU 1000 mg/m^2 96 hr continuous infusion; repeat the cycle every 28 days for 2–4 courses^Citation71 or docetaxel 60 mg/m^2 IV on day 1; DDP 60 mg/m^2, IV on day 1; 5-FU 600 mg/m^2, 120 hr continuous infusion; repeat the cycle every 3 weeks for three cycles before CCRT.^Citation72 (ii) Gemcitabine + Carboplatin (GC regimen)^Citation:48 Gemcitabine 1000 mg/m^2 IV on days 1 and 8; carboplatin AUC 5 IV on day 1; repeat the cycle every 21 days for 2–4 courses (iii) Docetaxel + Cisplatin (DP regimen)^Citation:49 Docetaxel 75 mg/m^2 IV and DDP 75 mg/m^2 IV on day 1; repeat the cycle every 21 days for 2–4 courses (iv) Cisplatin + Fluorouracil (PF regimen)^Citation:73 DDP 100 mg/m^2 IV on day 1; 5-FU 1000 mg/m^2 96 hr continuous infusion; repeat the cycle every 3 weeks for 3 cycles. (v) EGFR monoclonal antibody combined with CRT/RT^Citation:61 Cetuximab IV at a starting dose of 400 mg/m^2 on day 1 about 7–10 days before starting CRT/RT; further weekly infusion at a maintenance dose of 250 mg/m^2 used with CRT/RT.

Abbreviations: IMRT, intensity-modulated radiotherapy; ETW, every 3-weeks; CCRT, concurrent chemotherapy and radiotherapy.

Box 4: Treatment recommendations for recurrent or metastatic NPC

Recommendations Locally recurrent disease (i) The total dose of radiotherapy administered in patients with locally recurrent nasopharyngeal carcinoma (NPC) should be recalculated after considering the patient’s condition, the extent of tumor invasion, and tumor volume. At present, there is no consensus on the best dose fraction and total doses. Generally, larger dose fractions and the total dose lead to a higher local control rate, but also more toxicities. The local control rate of total dose ≥60 Gy with regular dose fractions is significantly better than <60 Gy.

Box 5: Treatment recommendations for recurrent/metastatic NPC not suitable for radiotherapy/surgery

Recommendations (a) Patients with Locally recurrent and metastatic nasopharyngeal carcinoma (NPC) who are not suitable for radiotherapy/surgery 1. GP regimen: Gemcitabine 1250 mg/m^2 IV on days 1 and 8; DDP 75 mg/m^2 IV on day 1; repeat the cycle every 21 days for 6 courses^Citation77 or gemcitabine 1000 mg/m^2 IV on days 1 and 8; DDP 80 mg/m^2 IV on day 1; repeat the cycle every 21 days for 6 courses.^Citation78 2. Docetaxel + Carboplatin [DC regimen]^Citation:79 Docetaxel 65 mg/m^2 IV on day 1; carboplatin AUC 6 IV on day 1; repeat the cycle every 21 days for 6 courses. 3. TC regimen^Citation:80 Paclitaxel 175 mg/m^2 IV on day 1; carboplatin AUC 6 IV on day 1; repeat the cycle every 21 days for 6 courses 4. TPF regimen^Citation:82 Paclitaxel 135 mg/m^2 IV on day 1; DDP 25 mg/m^2 IV on days 1 to day 3; 5-FU 600–1000 mg/m^2/day 120 hr continuous infusion; repeat the cycle every three weeks for 6 courses 5. CC regimen^Citation:85 Capecitabine 1000 mg/m^2 PO BID on days 1–14 and DDP 80 mg/m^2 IV on day 1; repeat the cycle every 21 days for 6 courses 6. Gemox regimen^Citation:86 Gemcitabine 1000 mg/m^2 continuous IV infusion at a constant rate of 10 mg/m^2·min on day 1; oxaliplatin 100 mg/m^2 IV on day 2; repeat the cycle every 14 days for 12 courses Regimen for resistant platinum-based chemotherapy 1. Gemcitabine regimen^Citation:88 Gemcitabine 1000 mg/m^2 IV on days 1, 8, and 15; repeat the cycle every 28 days for 6 courses 2. GN regimen^Citation:87 Gemcitabine 1000 mg/m^2 IV on days 1 and 8; vinorelbine 25 mg/m^2 IV on days 1 and 8; repeat the cycle every 21 days for 6 courses 3. Capecitabine regimen^Citation:89 Capecitabine 1250 mg/m^2 PO BID on days 1–14, repeat the cycle every 21 days 4. Docetaxel regimen^Citation:90 Docetaxel 30 mg/m^2 IV on days 1, 8, and 15, followed by 1 week rest; repeat the cycle every 28 days for 6 courses 5. Cetuximab + Carboplatin regimen^Citation:91 Cetuximab, IV at a starting dose of 400 mg/m^2 on day 1; further weekly infusion at a maintenance dose of 250 mg/m^2; carboplatin AUC 5 IV on day 1, repeat the cycle every 21 days for 6–8 courses

Al-Sarraf M, LeBlanc M, Giri PG, et al. Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: phase III randomized Intergroup study 0099. J Clin Oncol Off J Am Soc Clin Oncol. 1998;16(4):1310–1317. doi:10.1200/JCO.1998.16.4.1310

 PubMed Web of Science ®Google Scholar

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 Off J Am Soc Clin Oncol. 2005;23(27):6730–6738. doi:10.1200/JCO.2005.16.790

 PubMed Web of Science ®Google Scholar

Lee AWM, Tung SY, Chua DTT, et al. Randomized trial of radiotherapy plus concurrent-adjuvant chemotherapy vs radiotherapy alone for regionally advanced nasopharyngeal carcinoma. J Natl Cancer Inst. 2010;102(15):1188–1198. doi:10.1093/jnci/djq25820634482

 PubMed Web of Science ®Google Scholar

Chen L, Hu C-S, Chen X-Z, 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(2):163–171. doi:10.1016/S1470-2045(11)70320-522154591

 PubMed Web of Science ®Google Scholar

Dechaphunkul T, Pruegsanusak K, Sangthawan D, Sunpaweravong P. Concurrent chemoradiotherapy with carboplatin followed by carboplatin and 5-fluorouracil in locally advanced nasopharyngeal carcinoma. Head Neck Oncol. 2011;3:30. doi:10.1186/1758-3284-3-3021639934

 PubMedGoogle Scholar

Jin T, Zhang Q, Jiang F, et al. Neoadjuvant chemotherapy with different dose regimens of docetaxel, cisplatin and fluorouracil (TPF) for locoregionally advanced nasopharyngeal carcinoma: a retrospective study. Oncotarget. 2017;8:59. doi:10.18632/oncotarget.21992

 Google Scholar

Sun Y, Li W-F, Chen N-Y, et al. Induction chemotherapy plus concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: a phase 3, multicentre, randomised controlled trial. Lancet Oncol. 2016;17(11):1509–1520. doi:10.1016/S1470-2045(16)30410-727686945

 PubMed Web of Science ®Google Scholar

Lim AM, Corry J, Collins M, et al. A phase II study of induction carboplatin and gemcitabine followed by chemoradiotherapy for the treatment of locally advanced nasopharyngeal carcinoma. Oral Oncol. 2013;49(5):468–474. doi:10.1016/j.oraloncology.2012.12.01223369852

 PubMed Web of Science ®Google Scholar

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 Off J Am Soc Clin Oncol. 2009;27(2):242–249. doi:10.1200/JCO.2008.18.1545

 PubMed Web of Science ®Google Scholar

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. doi:10.1056/NEJMoa07095617960013

 PubMed Web of Science ®Google Scholar

Ma BBY, Kam MKM, Leung SF, et al. A phase II study of concurrent cetuximab-cisplatin and intensity-modulated radiotherapy in locoregionally advanced nasopharyngeal carcinoma. Ann Oncol Off J Eur Soc Med Oncol. 2012;23(5):1287–1292. doi:10.1093/annonc/mdr401

 PubMed Web of Science ®Google Scholar

Hsieh JC-H, Hsu C-L, Ng S-H, et al. Gemcitabine plus cisplatin for patients with recurrent or metastatic nasopharyngeal carcinoma in Taiwan: a multicenter prospective Phase II trial. Jpn J Clin Oncol. 2015;45(9):819–827. doi:10.1093/jjco/hyv08326056323

 PubMed Web of Science ®Google Scholar

Zhang L, Huang Y, Hong S, et al. Gemcitabine plus cisplatin versus fluorouracil plus cisplatin in recurrent or metastatic nasopharyngeal carcinoma: a multicentre, randomised, open-label, phase 3 trial. Lancet Lond Engl. 2016;388(10054):1883–1892. doi:10.1016/S0140-6736(16)31388-5

 PubMed Web of Science ®Google Scholar

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(3):182–188. doi:10.1080/0735790070120906117530488

 PubMed Web of Science ®Google Scholar

Tan EH, Khoo KS, Wee J, et al. Phase II trial of a paclitaxel and carboplatin combination in Asian patients with metastatic nasopharyngeal carcinoma. Ann Oncol Off J Eur Soc Med Oncol. 1999;10(2):235–237. doi:10.1023/A:1008390929826

 PubMed Web of Science ®Google Scholar

Chen C, Wang F, An X, et al. Triplet combination with paclitaxel, cisplatin and 5-FU is effective in metastatic and/or recurrent nasopharyngeal carcinoma. Cancer Chemother Pharmacol. 2013;71(2):371–378. doi:10.1007/s00280-012-2020-x23143190

 PubMed Web of Science ®Google Scholar

Li Y-H, Wang F-H, Jiang W-Q, et al. Phase II study of capecitabine and cisplatin combination as first-line chemotherapy in Chinese patients with metastatic nasopharyngeal carcinoma. Cancer Chemother Pharmacol. 2008;62(3):539–544. doi:10.1007/s00280-007-0641-218172651

 PubMed Web of Science ®Google Scholar

Ma BBY, Hui EP, Wong SCC, et al. Multicenter phase II study of gemcitabine and oxaliplatin in advanced nasopharyngeal carcinoma–correlation with excision repair cross-complementing-1 polymorphisms. Ann Oncol Off J Eur Soc Med Oncol. 2009;20(11):1854–1859. doi:10.1093/annonc/mdp065

 PubMed Web of Science ®Google Scholar

Zhang L, Zhang Y, Huang P-Y, Xu F, Peng P-J, Guan -Z-Z. 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):33–38. doi:10.1007/s00280-007-0441-817909810

 PubMed Web of Science ®Google Scholar

Chen C, Wang F, Wang Z, et al. Salvage gemcitabine-vinorelbine chemotherapy in patients with metastatic nasopharyngeal carcinoma pretreated with platinum-based chemotherapy. Oral Oncol. 2012;48(11):1146–1151. doi:10.1016/j.oraloncology.2012.05.02122748450

 PubMed Web of Science ®Google Scholar

Chua DTT, Sham JST, Au GKH. A phase II study of capecitabine in patients with recurrent and metastatic nasopharyngeal carcinoma pretreated with platinum-based chemotherapy. Oral Oncol. 2003;39(4):361–366.12676255

 PubMed Web of Science ®Google Scholar

Ngeow J, Lim WT, Leong SS, et al. Docetaxel is effective in heavily pretreated patients with disseminated nasopharyngeal carcinoma. Ann Oncol Off J Eur Soc Med Oncol. 2011;22(3):718–722. doi:10.1093/annonc/mdq425

 PubMed Web of Science ®Google Scholar

Chan ATC, Hsu -M-M, 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 Off J Am Soc Clin Oncol. 2005;23(15):3568–3576. doi:10.1200/JCO.2005.02.147

 PubMed Web of Science ®Google Scholar