Nasopharyngeal Cancer Treatment Protocols 

Nasopharyngeal Cancer Treatment Protocols 

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Treatment protocols for nasopharyngeal cancers are provided below, including generalized first-line therapy based on stage; chemoradiation therapy and induction chemotherapy for locally advanced disease; and first-, second-, and third-line chemotherapy for metastatic or recurrent disease. [1, 2, 3]

See the list below:

Treatment plans for all disease stages should be discussed at a multidisciplinary tumor conference involving ear, nose, throat (ENT) surgeons; radiation oncologists; and medical oncologists

Selected patients with advanced or metastatic disease may receive additional therapy (radiation or neck dissection) depending on their response to first-line therapy

Surgery at the primary disease site has a very limited role, if any, in nasopharyngeal cancers

Stage I:

Patients with early or localized disease may be treated with definitive radiation therapy to the nasopharynx alone

Radiation doses of 66-70 Gy (2.0 Gy/fraction; daily Monday-Friday in 7wk)

Stages II-IVB:

Patients with stage II-IVB nasopharyngeal cancers are treated with concurrent chemotherapy and radiation +/- adjuvant chemotherapy or with induction chemotherapy followed by concurrent chemoradiation

Acceptable chemotherapy regimens for advanced nasopharyngeal cancers (stages II-IVB):

Cisplatin 100 mg/m2 IV on days 1, 22, and 43 with radiation +/- adjuvant chemotherapy with cisplatin 80 mg/m2 IV on day 1 plus fluorouracil (5-FU) 1000 mg/m2/day by continuous IV infusion on days 1-4 every 4wk for 3 cycles [4, 5, 6] or

Carboplatin AUC 6 IV every 3 weeks for 3 cycles with radiation +/- adjuvant chemotherapy with carboplatin AUC 5 IV on day 1 plus  fluorouracil (5-FU) 1000 mg/m2/day by continuous IV infusion on days 1-4 every 3 weeks for 2 cycles [7]

Radiation doses during concurrent chemoradiation are up to 70 Gy (2.0 Gy/fraction)

Induction chemotherapy with docetaxel 70 mg/m2 IV on day 1 plus  cisplatin 75 mg/m2 IV on day 1 plus  5-FU 1000 mg/m2/day by continuous IV infusion on days 1-4 for three cycles followed by concurrent chemoradiation with cisplatin 100 mg/m2 IV on days 1, 22, and 43  [8]

Stage IVC:

Patients with metastatic nasopharyngeal cancers or recurrent disease (after first-line therapy) are treated with standard platinum-based chemotherapies

Single agents can be used if patients cannot tolerate platinum-based agents [9, 10]

Acceptable chemotherapy regimens in patients with metastatic, progressing, or recurrent nasopharyngeal cancers (unless otherwise stated, goal is to complete 4-6 cycles):

Cisplatin 75 mg/m2 IV on day 1 plus docetaxel 75 mg/m2 IV on day 1 every 3wk [11, 12, 13] or

Cisplatin 75 mg/m2 IV on day 1 plus paclitaxel 175 mg/m2 IV on day 1 every 3wk [14, 15] or

Carboplatin area under the curve (AUC; see the Carboplatin AUC Dose Calculation [Calvert formula] calculator) 6 IV on day 1 plus  docetaxel 65 mg/m2 IV on day 1 every 3wk [16] or

Carboplatin AUC 6 IV on day 1 plus  paclitaxel 200 mg/m2 IV on day 1 every 3wk [17, 18, 19] or

Cisplatin 100 mg/m2 IV on day 1 plus  5-FU 1000 mg/m2/day by continuous IV infusion on days 1-4 every 3wk [20, 15, 21, 22, 23] or

Cisplatin 50-70 mg/m2 IV on day 1 plus gemcitabine 1000 mg/m2 IV on days 1, 8, and 15 every 4wk [24, 25] or

Cetuximab 400 mg/m2 IV on day 1 followed by 250 mg/m2 IV weekly plus  carboplatin AUC 5 IV every 3 weeks for up to 8 cycles [26] or 

Gemcitabine 1000 mg/m2 IV plus  vinorelbine 25 mg/m2 IV on days 1 and 8 every 21 days [27] or

Gemcitabine 1000 mg/m2 IV on days 1, 8, and 15 every 4wk [24, 28] or

Gemcitabine 1250 mg/m2 IV on days 1 and 8 every 3wk [29] or

Methotrexate 40 mg/m2 IV weekly (3wk equals 1 cycle) [10, 20] or

Paclitaxel 200 mg/m2 IV every 3wk [30] or

Docetaxel 75 mg/m2 IV every 3wk [31, 32, 33, 34, 35]

Stage IVC:

Second-line chemotherapy is given after disease progression or recurrence following completion of first-line therapy

Third-line therapies are given after disease progression or recurrence following completion of first- and second-line therapies

Second- and third-line regimens are similar to regimens used as first-line therapy but usually offer lower response rates and survival benefits

Patients should be treated with platinum-based chemotherapies if they have not previously received a platinum-based drug

Some regimens are typically used in head and neck cancers in general, and others have been specifically studied in nasopharyngeal cancer [9, 10]

Acceptable chemotherapy regimens in patients with metastastic, progressing or recurrent nasopharyngeal cancers after completion of first-line therapy:

Cisplatin 75 mg/m2 IV on day 1 plus  docetaxel 75 mg/m2 IV on day 1 every 3wk [11] or

Cisplatin 75 mg/m2 IV on day 1 plus  paclitaxel 175 mg/m2 IV on day 1 every 3wk [14, 15] or

Carboplatin AUC 6 IV on day 1 plus  docetaxel 65 mg/m2 IV on day 1 every 3wk [16] or

Carboplatin AUC 6 IV on day 1 plus  paclitaxel 200 mg/m2 IV on day 1 every 3wk [17, 19, 36] or

Cisplatin 100 mg/m2 IV on day 1 plus  5-FU 1000 mg/m2/day by continuous IV infusion on days 1-4 every 3wk [20, 15, 21, 22, 23] or

Cisplatin 50-70 mg/m2 IV on day 1 plus  gemcitabine 1000 mg/m2 IV on days 1, 8, and 15 every 4wk [24, 25] or

Cetuximab 400 mg/m2 IV on day 1 followed by 250 mg/m2 IV weekly plus  carboplatin AUC 5 IV every 3 weeks for up to 8 cycles [26] or 

Gemcitabine 1000 mg/m2 IV plus  vinorelbine 25 mg/m2 IV on days 1 and 8 every 21 days [27] or

Gemcitabine 1000 mg/m2 IV on days 1, 8, and 15 every 4wk or

Gemcitabine 1250 mg/m2 IV on days 1 and 8 every 3wk [24, 28] or

Methotrexate 40 mg/m2 IV weekly (3wk equals 1 cycle) or

Paclitaxel 200 mg/m2 IV every 3wk [30] or

Docetaxel 75 mg/m2 IV every 3wk [31, 32, 33, 34, 35]

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Al-Sarraf M, LeBlanc M, Giri PG, et al. Superiority of five year survival with chemo-radiotherapy (CT-RT) vs radiotherapy in patients (Pts) with locally advanced nasopharyngeal cancer (NPC). Intergroup (0099) (SWOG 8892, RTOG 8817, ECOG 2388) Phase III Study: Final Report. Presented at: Annual Meeting of ASCO; 2001.

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Lee AW, Lau WH, Tung SY, Chua DT, Chappell R, Xu L, et al. Preliminary results of a randomized study on therapeutic gain by concurrent chemotherapy for regionally-advanced nasopharyngeal carcinoma: NPC-9901 Trial by the Hong Kong Nasopharyngeal Cancer Study Group. J Clin Oncol. 2005 Oct 1. 23(28):6966-75. [Medline].

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 Jun 5. 3:30. [Medline].

Bae WK, Hwang JE, Shim HJ, Cho SH, Lee JK, Lim SC, 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 Feb. 65 (3):589-95. [Medline].

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National Comprehensive Cancer Network. National Comprehensive Cancer Network Guidelines. Head and Neck Cancers V 1.2015. Available at http://www.nccn.org/professionals/physician_gls/pdf/head-and-neck.pdf. Accessed: December 31, 2015.

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McCarthy JS, Tannock IF, Degendorfer P, Panzarella T, Furlan M, Siu LL. A Phase II trial of docetaxel and cisplatin in patients with recurrent or metastatic nasopharyngeal carcinoma. Oral Oncol. 2002 Oct. 38(7):686-90. [Medline].

Chua DT, Sham JS, Au GK. A phase II study of docetaxel and cisplatin as first-line chemotherapy in patients with metastatic nasopharyngeal carcinoma. Oral Oncol. 2005 Jul. 41(6):589-95. [Medline].

Forastiere AA, Leong T, Rowinsky E, Murphy BA, Vlock DR, DeConti RC, et al. Phase III comparison of high-dose paclitaxel + cisplatin + granulocyte colony-stimulating factor versus low-dose paclitaxel + cisplatin in advanced head and neck cancer: Eastern Cooperative Oncology Group Study E1393. J Clin Oncol. 2001 Feb 15. 19(4):1088-95. [Medline].

Gibson MK, Li Y, Murphy B, Hussain MH, DeConti RC, Ensley J, 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 May 20. 23(15):3562-7. [Medline].

Samlowski WE, Moon J, Kuebler JP, Nichols CR, Gandara DR, Ozer H, 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 Apr-May. 25(3):182-8. [Medline].

Airoldi M, Pedani F, Marchionatti S, Gabriele AM, Succo G, Gabriele P, et al. Carboplatin plus taxol is an effective third-line regimen in recurrent undifferentiated nasopharyngeal carcinoma. Tumori. 2002 Jul-Aug. 88(4):273-6. [Medline].

Tan EH, Khoo KS, Wee J, Fong KW, Lee KS, Lee KM, et al. Phase II trial of a paclitaxel and carboplatin combination in Asian patients with metastatic nasopharyngeal carcinoma. Ann Oncol. 1999 Feb. 10(2):235-7. [Medline].

Ciuleanu TE, Fountzilas G, Ciuleanu E, Plataniotis M, Todor N, Ghilezan N. Paclitaxel and carboplatin in relapsed or metastatic nasopharyngeal carcinoma: a multicenter phase II study. J BUON. 2004 Apr-Jun. 9(2):161-5. [Medline].

A phase III randomised trial of cisplatinum, methotrextate, cisplatinum + methotrexate and cisplatinum + 5-FU in end stage squamous carcinoma of the head and neck. Liverpool Head and Neck Oncology Group. Br J Cancer. 1990 Feb. 61(2):311-5. [Medline]. [Full Text].

Forastiere AA, Metch B, Schuller DE, Ensley JF, Hutchins LF, Triozzi P, 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. [Medline].

Jacobs C, Lyman G, Velez-García E, Sridhar KS, Knight W, Hochster H, 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 Feb. 10(2):257-63. [Medline].

Clavel M, Vermorken JB, Cognetti F, Cappelaere P, de Mulder PH, Schornagel JH, et al. Randomized comparison of cisplatin, methotrexate, bleomycin and vincristine (CABO) versus cisplatin and 5-fluorouracil (CF) versus cisplatin (C) in recurrent or metastatic squamous cell carcinoma of the head and neck. A phase III study of the EORTC Head and Neck Cancer Cooperative Group. Ann Oncol. 1994 Jul. 5(6):521-6. [Medline].

Ma BB, Tannock IF, Pond GR, Edmonds MR, Siu LL. Chemotherapy with gemcitabine-containing regimens for locally recurrent or metastatic nasopharyngeal carcinoma. Cancer. 2002 Dec 15. 95(12):2516-23. [Medline].

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Chan AT, Hsu MM, Goh BC, Hui EP, Liu TW, Millward MJ, et al. Multicenter, phase II study of cetuximab in combination with carboplatin in patients with recurrent or metastatic nasopharyngeal carcinoma. J Clin Oncol. 2005 May 20. 23 (15):3568-76. [Medline].

Chen C, Wang FH, Wang ZQ, An X, Luo HY, Zhang L, et al. Salvage gemcitabine-vinorelbine chemotherapy in patients with metastatic nasopharyngeal carcinoma pretreated with platinum-based chemotherapy. Oral Oncol. 2012 Nov. 48 (11):1146-51. [Medline].

Zhang L, Zhang Y, Huang PY, Xu F, Peng PJ, Guan ZZ. 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 Jan. 61(1):33-8. [Medline].

Ngan RK, Yiu HH, Lau WH, Yau S, Cheung FY, Chan TM, et al. Combination gemcitabine and cisplatin chemotherapy for metastatic or recurrent nasopharyngeal carcinoma: report of a phase II study. Ann Oncol. 2002 Aug. 13(8):1252-8. [Medline].

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Catimel G, Verweij J, Mattijssen V, Hanauske A, Piccart M, Wanders J, et al. Docetaxel (Taxotere): an active drug for the treatment of patients with advanced squamous cell carcinoma of the head and neck. EORTC Early Clinical Trials Group. Ann Oncol. 1994 Jul. 5(6):533-7. [Medline].

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Couteau C, Chouaki N, Leyvraz S, Oulid-Aissa D, Lebecq A, Domenge C, et al. A phase II study of docetaxel in patients with metastatic squamous cell carcinoma of the head and neck. Br J Cancer. 1999 Oct. 81(3):457-62. [Medline]. [Full Text].

Guardiola E, Peyrade F, Chaigneau L, Cupissol D, Tchiknavorian X, Bompas E, et al. Results of a randomised phase II study comparing docetaxel with methotrexate in patients with recurrent head and neck cancer. Eur J Cancer. 2004 Sep. 40(14):2071-6. [Medline].

Zenda S, Onozawa Y, Boku N, Iida Y, Ebihara M, Onitsuka T. Single-agent docetaxel in patients with platinum-refractory metastatic or recurrent squamous cell carcinoma of the head and neck (SCCHN). Jpn J Clin Oncol. 2007 Jul. 37(7):477-81. [Medline].

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Lee AW, Sze WM, Au JS, Leung SF, Leung TW, Chua DT, et al. Treatment results for nasopharyngeal carcinoma in the modern era: the Hong Kong experience. Int J Radiat Oncol Biol Phys. 2005 Mar 15. 61(4):1107-16. [Medline].

Peng X, Zhang Q, Zeng Y, Li J, Wang L, Ai P. Evodiamine inhibits the migration and invasion of nasopharyngeal carcinoma cells in vitro via repressing MMP-2 expression. Cancer Chemother Pharmacol. 2015 Dec. 76 (6):1173-84. [Medline].

Marvaretta M Stevenson, MD Assistant Professor, Division of Medical Oncology, Duke University Medical Center

Disclosure: Nothing to disclose.

Jasmeet Anand, PharmD, RPh Adjunct Instructor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Christopher D Braden, DO Hematologist/Oncologist, Chancellor Center for Oncology at Deaconess Hospital; Medical Director, Deaconess Hospital Outpatient Infusion Centers; Chairman, Deaconess Hospital Cancer Committee

Christopher D Braden, DO is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology

Disclosure: Nothing to disclose.

Guy J Petruzzelli, MD, PhD, MBA, FACS Physician-in-Chief and Vice President of Oncology Programs, Curtis and Elizabeth Anderson Cancer Institute at Memorial University Medical Center; Professor of Surgery-Head, Neck, and Endocrine Surgery, Mercer University School of Medicine-Savannah Campus

Guy J Petruzzelli, MD, PhD, MBA, FACS is a member of the following medical societies: American Academy of Otolaryngology-Head and Neck Surgery, American Association for the Advancement of Science, American Association of Clinical Anatomists, American College of Surgeons, American Head and Neck Society, American Medical Association, American Society of Clinical Oncology, Chicago Medical Society, Georgia Society of Otolaryngology-Head and Neck Surgery, International Academy of Oral Oncology, International Head and Neck Scientific Group, North American Skull Base Society, Society of Surgical Oncology, Society of University Otolaryngologists-Head and Neck Surgeons, SWOG

Disclosure: Nothing to disclose.

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