Nasopharyngeal Cancer Treatment (PDQ®): Treatment - Health Professional Information [NCI]

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Nasopharyngeal Cancer Treatment

General Information About Nasopharyngeal Cancer

Anatomy

The nasopharynx has a cuboidal shape. The lateral walls are formed by the eustachian tube and the fossa of Rosenmuller. The roof, sloping downward from anterior to posterior, is bordered by the pharyngeal hypophysis, pharyngeal tonsil, and pharyngeal bursa with the base of the skull above. Anteriorly, the nasopharynx abuts the posterior choanae and nasal cavity, and the posterior boundary is formed by the muscles of the posterior pharyngeal wall. Inferiorly, the nasopharynx ends at an imaginary horizontal line formed by the upper surface of the soft palate and the posterior pharyngeal wall.

Risk Factors

Unlike other squamous cell cancers of the head and neck, nasopharyngeal cancer does not appear to be linked to excess use of tobacco or moderate alcohol intake (up to 15 drinks a week). Factors thought to predispose to this tumor include the following:

  • Chinese (or Asian) ancestry.[1]
  • Epstein-Barr virus (EBV) exposure.
  • Unknown factors that result in very rare familial clusters.[2]
  • Heavy alcohol intake.[3]

Signs and Symptoms

Symptoms and signs at presentation include the following:

  • Painless, enlarged lymph nodes in the neck (present in approximately 75% of patients and often bilateral and posterior).
  • Nasal obstruction.
  • Epistaxis.
  • Diminished hearing.
  • Tinnitus.
  • Recurrent otitis media.
  • Cranial nerve dysfunction (usually II–VI or IX–XII).
  • Sore throat.
  • Headache.

In the patient who presents with only cervical adenopathy, the finding of EBV genomic material in the tissue after amplification of DNA with the polymerase chain reaction lends strong evidence for a nasopharyngeal primary tumor, and a concerted search should be conducted in that area.[4]

Diagnostic Tests

Diagnosis is made by biopsy of the nasopharyngeal mass. Workup includes the following:[5]

  • Careful visual examination (by fiberoptic endoscopic examination or examination under anesthesia [EUA]).
  • Documentation of the size and location of the tumor and neck nodes.
  • Evaluation of cranial nerve function including neuro-ophthalmological evaluation and audiological evaluation.
  • Computed tomographic (CT) scan or positron emission tomography (PET)-CT scan.
  • Magnetic resonance imaging (MRI) to evaluate skull base invasion.
  • Hemogram.
  • Chemistry panel.
  • Epstein-Barr virus titers.

Any clinical or laboratory suggestion of distant metastasis may prompt further evaluation of other sites. Careful dental and oral hygiene evaluation and therapy is particularly important prior to initiation of radiation treatment. MRI is often more helpful than CT scans in assessing skull base involvement and in defining the extent of abnormalities detected.[5,6,7]

Prognosis

Major prognostic factors adversely influencing outcome of treatment include the following:[8]

  • Large tumor size.[9][Level of evidence: 3iiiA]
  • A higher tumor (T) stage.
  • The presence of involved neck nodes.

Other factors linked to diminished survival that were present in some, but not all, studies include the following:

  • Age.
  • World Health Organization (WHO) grade I.
  • Long interval between biopsy and initiation of radiation therapy.
  • Diminished immune function at diagnosis.
  • Incomplete excision of involved neck nodes.
  • Pregnancy during treatment.
  • Locoregional relapse.
  • Certain EBV antibody titer patterns.

Small cancers of the nasopharynx are highly curable by radiation therapy, and patients with these small cancers have shown survival rates of 80% to 90%.[10]

Moderately advanced lesions without clinical evidence of spread to cervical lymph nodes are often curable, and patients with these lesions have shown survival rates of 50% to 70%.

Follow-up

Follow-up for patients includes the following:

  • Routine periodic examination of the original tumor site and neck.
  • CT or PET-CT scan.
  • MRI scan.
  • Blood work.
  • EBV titers.

Monitoring of patients should include the following:

  • Surveillance of thyroid and pituitary function.
  • Dental and oral hygiene.
  • Jaw exercises to avoid trismus.
  • Evaluation of cranial nerve function, especially as it relates to vision and hearing.
  • Evaluation of systemic complaints to identify distant metastasis.

Although most recurrences occur within 5 years of diagnosis, relapse can be seen at longer intervals. The incidence of second primary malignancies is less than after treatment of tumors at other head and neck sites.[11]

Poorly differentiated squamous cell cancer has been associated with EBV antibodies.[4,12] High-titer antibodies to virus capsid antigen and early antigen, especially of high IgA class, or high titers that persist after therapy, have been associated with a poorer prognosis.[13] This finding remains under evaluation.

Tumors of many histologies can occur in the nasopharynx, but this discussion, like the American Joint Committee on Cancer nasopharynx staging, refers exclusively to WHO grade I-, II-, and III-type nasopharyngeal carcinoma.

References:

1. Chien YC, Chen JY, Liu MY, et al.: Serologic markers of Epstein-Barr virus infection and nasopharyngeal carcinoma in Taiwanese men. N Engl J Med 345 (26): 1877-82, 2001.
2. Decker J, Goldstein JC: Risk factors in head and neck cancer. N Engl J Med 306 (19): 1151-5, 1982.
3. Chen L, Gallicchio L, Boyd-Lindsley K, et al.: Alcohol consumption and the risk of nasopharyngeal carcinoma: a systematic review. Nutr Cancer 61 (1): 1-15, 2009.
4. Feinmesser R, Miyazaki I, Cheung R, et al.: Diagnosis of nasopharyngeal carcinoma by DNA amplification of tissue obtained by fine-needle aspiration. N Engl J Med 326 (1): 17-21, 1992.
5. Cummings CW, Fredrickson JM, Harker LA, et al.: Otolaryngology - Head and Neck Surgery. Saint Louis, Mo: Mosby-Year Book, Inc., 1998.
6. Mendenhall WM, Werning JW, Pfister DG: Treatment of head and neck cancer. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2011, pp 729-80.
7. Laramore GE, ed.: Radiation Therapy of Head and Neck Cancer. Berlin: Springer-Verlag, 1989.
8. 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 37 (5): 985-96, 1997.
9. Lee CC, Huang TT, Lee MS, et al.: Clinical application of tumor volume in advanced nasopharyngeal carcinoma to predict outcome. Radiat Oncol 5: 20, 2010.
10. Bailet JW, Mark RJ, Abemayor E, et al.: Nasopharyngeal carcinoma: treatment results with primary radiation therapy. Laryngoscope 102 (9): 965-72, 1992.
11. Cooper JS, Scott C, Marcial V, et al.: The relationship of nasopharyngeal carcinomas and second independent malignancies based on the Radiation Therapy Oncology Group experience. Cancer 67 (6): 1673-7, 1991.
12. Neel HB 3rd, Pearson GR, Taylor WF: Antibodies to Epstein-Barr virus in patients with nasopharyngeal carcinoma and in comparison groups. Ann Otol Rhinol Laryngol 93 (5 Pt 1): 477-82, 1984 Sep-Oct.
13. Lin JC, Chen KY, Wang WY, et al.: Detection of Epstein-Barr virus DNA the peripheral-blood cells of patients with nasopharyngeal carcinoma: relationship to distant metastasis and survival. J Clin Oncol 19 (10): 2607-15, 2001.

Cellular Classification of Nasopharyngeal Cancer

Although a wide variety of malignant tumors may arise in the nasopharynx, only squamous cell carcinoma is considered in this discussion because management of the other types varies substantially with histology. Subdivisions of squamous cell carcinoma in this site include the following:

World Health Organization (WHO) histopathological grading system describes three types of nasopharyngeal cancer:

1. Keratinizing squamous cell carcinoma.
2. Nonkeratinizing squamous cell carcinoma.
3. Undifferentiated carcinoma (most common subtype).

Previous subdivisions of nasopharyngeal carcinoma included lymphoepithelioma, which is now classified as WHO grade III characterized by lymphoid infiltrate.[1]

WHO grade I-type cancer accounts for 20% of cases in United States and is associated with alcohol and tobacco use; WHO grade II and III represent the endemic form seen in Southern China.

The presence of keratin has been associated with reduced local control and survival.

References:

1. Shanmugaratnam K, Sobin L: Histological Typing of Upper Respiratory Tract Tumours. Geneva: World Health Organization, 1978. International Histologic Classification of Tumours: No. 19.

Stage Information for Nasopharyngeal Cancer

Staging systems are all clinical staging and are based on the best possible estimate of the extent of disease before treatment.[1,2] Assessment of the primary tumor is based on inspection and palpation, and fiberoptic endoscopic evaluation. The tumor must be confirmed histologically, and any other pathologic data obtained on biopsy may be included. Evaluation of the function of the cranial nerves is especially appropriate for tumors of the nasopharynx. The appropriate nodal drainage areas are examined by careful palpation and radiologic evaluation. The retropharyngeal lymph nodes are the first echelon of drainage.[3,4] Information from diagnostic imaging studies may be used in staging. Magnetic resonance imaging provides additional information to computed tomographic scanning in the evaluation of skull base invasion and intracranial spread.[5] Positron emission tomography scans combined with CT are helpful in radiation treatment planning for target delineation of the primary tumor, aids in detection of metastatic nodal involvement and metastatic spread such as lung or skeletal metastases in patients with advanced nasopharyngeal cancer.[6]

If a patient has a relapse, a complete reassessment must be done to select the appropriate additional therapy.

Definitions of TNM

The American Joint Committee on Cancer (AJCC) has designated staging by TNM classification to define nasopharyngeal cancer.[7]

Table 1. Primary Tumor (T)a

a Reprinted with permission from AJCC: Pharynx. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 41-56.
b Parapharyngeal extension denotes posterolateral infiltration of tumor.
TX Primary tumor cannot be assessed.
T0 No evidence of primary tumor.
Tis Carcinomain situ.
T1 Tumor confined to the nasopharynx, or tumor extends to oropharynx and/or nasal cavity without parapharyngeal extension.b
T2 Tumor with parapharyngeal extension.b
T3 Tumor involves bony structures of skull base and/or paranasal sinuses.
T4 Tumor with intracranial extension and/or involvement of cranial nerves, hypopharynx, orbit, or with extension to the infratemporal fossa/masticator space.

Table 2. Regional Lymph Nodes (N)a, b

a Reprinted with permission from AJCC: Pharynx. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 44-56.
b The distribution and the prognostic impact of regional lymph node spread from nasopharyngeal cancer, particularly of the undifferentiated type, are different from those of other head and neck mucosal cancers and justify the use of a different N classification scheme.
c Midline nodes are considered ipsilateral nodes.
d Supraclavicular zone or fossa is relevant to the staging of nasopharyngeal carcinoma and is the triangular region originally described by Ho. It is defined by three points: (1) the superior margin of the sternal end of the clavicle, (2) the superior margin of the lateral end of the clavicle, (3) the point where the neck meets the shoulder. Note that this would include caudal portions of levels IV and VB. All cases with lymph nodes (whole or part) in the fossa are considered N3b.
NX Regional lymph nodes cannot be assessed.
N0 No regional lymph node metastasis.
N1 Unilateral metastasis in cervical lymph node(s), ≤6 cm in greatest dimension, above the supraclavicular fossa, and/or unilateral or bilateral, retropharyngeal lymph nodes, ≤6 cm in greatest dimension.c
N2 Bilateral metastasis in cervical lymph node(s), ≤6 cm in greatest dimension, above the supraclavicular fossa.d
N3 Metastasis in a lymph node(s)c>6 cm and/or to supraclavicular fossa.d
N3a >6 cm in dimension.
N3b Extension to the supraclavicular fossa.d

Table 3. Distant Metastasis (M)a

a Reprinted with permission from AJCC: Pharynx. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 41-56.
M0 No distant metastasis.
M1 Distant metastasis.

Table 4. Anatomic Stage/Prognostic Groupsa

Stage T N M
a Reprinted with permission from AJCC: Pharynx. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 41-56.
0 Tis N0 M0
I T1 N0 M0
II T1 N1 M0
T2 N0 M0
T2 N1 M0
III T1 N2 M0
T2 N2 M0
T3 N0 M0
T3 N1 M0
T3 N2 M0
IVA T4 N0 M0
T4 N1 M0
T4 N2 M0
IVB Any T N3 M0
IVC Any T Any N M1

References:

1. Teo PM, Leung SF, Yu P, et al.: A comparison of Ho's, International Union Against Cancer, and American Joint Committee stage classifications for nasopharyngeal carcinoma. Cancer 67 (2): 434-9, 1991.
2. Lee AW, Foo W, Law SC, et al.: Staging of nasopharyngeal carcinoma: from Ho's to the new UICC system. Int J Cancer 84 (2): 179-87, 1999.
3. Mendenhall WM, Werning JW, Pfister DG: Treatment of head and neck cancer. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2011, pp 729-80.
4. Laramore GE, ed.: Radiation Therapy of Head and Neck Cancer. Berlin: Springer-Verlag, 1989.
5. Consensus conference. Magnetic resonance imaging. JAMA 259 (14): 2132-8, 1988.
6. Liu FY, Chang JT, Wang HM, et al.: [18F]fluorodeoxyglucose positron emission tomography is more sensitive than skeletal scintigraphy for detecting bone metastasis in endemic nasopharyngeal carcinoma at initial staging. J Clin Oncol 24 (4): 599-604, 2006.
7. Pharynx. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 41-56.

Treatment Option Overview

Standard treatments for patients with nasopharyngeal cancer include the following:

  • Radiation therapy alone.
  • Concurrent chemoradiation followed by adjuvant chemotherapy.
  • Surgery for residual nodal disease.
  • Chemotherapy alone for metastatic disease.

High-dose radiation therapy with chemotherapy is the primary treatment of nasopharyngeal cancer, both for the primary tumor site and the neck.[1] When feasible, surgery is usually reserved for nodes that fail to regress after radiation therapy or for nodal recurrence following clinical complete response. Radiation therapy dose and field margins are individually tailored to the location and size of the primary tumor and lymph nodes.[2,3,4,5] Although most tumors are treated with external-beam radiation therapy (EBRT) exclusively, in some tumors radiation therapy may be boosted with intracavitary or interstitial implants or by the use of stereotactic radiosurgery when clinical expertise is available, and the anatomy is suitable.[6,7,8,9,10] Intensity-modulated radiation therapy (IMRT) results in a lower incidence of xerostomia and may provide a better quality of life than conventional three-dimensional or two-dimensional radiation therapy.[11,12][Level of evidence: 1iiC] Results of a phase II RTOG study (RTOG-0225) showed the feasibility of IMRT in a multi-institutional setting and minimal grade III and IV xerostomia rates.[13] The rate of grade 2 xerostomia at 1 year from start of IMRT was 13.5%. Only 2 of 68 patients were reported with grade 3 xerostomia, and none had grade 4 xerostomia.[13][Level of evidence: 2C]

Accumulating evidence has demonstrated a high incidence (>30%–40%) of hypothyroidism in patients who have received radiation therapy that delivered EBRT to the entire thyroid gland or to the pituitary gland. Thyroid-function testing of patients should be considered prior to therapy and as part of posttreatment follow-up.[14,15]

Treatments under clinical evaluation for patients with nasopharyngeal cancer include the following:

  • Dose escalation with new radiation therapy techniques such as stereotactic radiation therapy boost.[16][Level of evidence: 3iiiDiv]
  • Brachytherapy.[17][Level of evidence: 3iiiDii]

Information about ongoing clinical trials is available from the NCI Web site.

References:

1. Baujat B, Audry H, Bourhis J, et al.: Chemotherapy in locally advanced nasopharyngeal carcinoma: an individual patient data meta-analysis of eight randomized trials and 1753 patients. Int J Radiat Oncol Biol Phys 64 (1): 47-56, 2006.
2. Perez CA, Devineni VR, Marcial-Vega V, et al.: Carcinoma of the nasopharynx: factors affecting prognosis. Int J Radiat Oncol Biol Phys 23 (2): 271-80, 1992.
3. Lee AW, Law SC, Foo W, et al.: Nasopharyngeal carcinoma: local control by megavoltage irradiation. Br J Radiol 66 (786): 528-36, 1993.
4. Geara FB, Sanguineti G, Tucker SL, et al.: Carcinoma of the nasopharynx treated by radiotherapy alone: determinants of distant metastasis and survival. Radiother Oncol 43 (1): 53-61, 1997.
5. 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 37 (5): 985-96, 1997.
6. Mendenhall WM, Werning JW, Pfister DG: Treatment of head and neck cancer. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2011, pp 729-80.
7. Itami J, Anzai Y, Nemoto K, et al.: Prognostic factors for local control in nasopharyngeal cancer (NPC): analysis by multivariate proportional hazard models. Radiother Oncol 21 (4): 233-9, 1991.
8. Levendag PC, Schmitz PI, Jansen PP, et al.: Fractionated high-dose-rate brachytherapy in primary carcinoma of the nasopharynx. J Clin Oncol 16 (6): 2213-20, 1998.
9. Teo PM, Leung SF, Lee WY, et al.: Intracavitary brachytherapy significantly enhances local control of early T-stage nasopharyngeal carcinoma: the existence of a dose-tumor-control relationship above conventional tumoricidal dose. Int J Radiat Oncol Biol Phys 46 (2): 445-58, 2000.
10. Le QT, Tate D, Koong A, et al.: Improved local control with stereotactic radiosurgical boost in patients with nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys 56 (4): 1046-54, 2003.
11. Pow EH, Kwong DL, McMillan AS, et al.: Xerostomia and quality of life after intensity-modulated radiotherapy vs. conventional radiotherapy for early-stage nasopharyngeal carcinoma: initial report on a randomized controlled clinical trial. Int J Radiat Oncol Biol Phys 66 (4): 981-91, 2006.
12. Kam MK, Leung SF, Zee B, et al.: Prospective randomized study of intensity-modulated radiotherapy on salivary gland function in early-stage nasopharyngeal carcinoma patients. J Clin Oncol 25 (31): 4873-9, 2007.
13. Lee N, Harris J, Garden AS, et al.: Intensity-modulated radiation therapy with or without chemotherapy for nasopharyngeal carcinoma: radiation therapy oncology group phase II trial 0225. J Clin Oncol 27 (22): 3684-90, 2009.
14. Turner SL, Tiver KW, Boyages SC: Thyroid dysfunction following radiotherapy for head and neck cancer. Int J Radiat Oncol Biol Phys 31 (2): 279-83, 1995.
15. Constine LS: What else don't we know about the late effects of radiation in patients treated for head and neck cancer? Int J Radiat Oncol Biol Phys 31 (2): 427-9, 1995.
16. Tate DJ, Adler JR Jr, Chang SD, et al.: Stereotactic radiosurgical boost following radiotherapy in primary nasopharyngeal carcinoma: impact on local control. Int J Radiat Oncol Biol Phys 45 (4): 915-21, 1999.
17. Lu JJ, Shakespeare TP, Tan LK, et al.: Adjuvant fractionated high-dose-rate intracavitary brachytherapy after external beam radiotherapy in Tl and T2 nasopharyngeal carcinoma. Head Neck 26 (5): 389-95, 2004.

Stage I Nasopharyngeal Cancer

Standard treatment options:

  • High-dose radiation therapy to the primary tumor site and prophylactic radiation therapy to the nodal drainage.[1]

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage I nasopharyngeal cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

1. Xiao WW, Han F, Lu TX, et al.: Treatment outcomes after radiotherapy alone for patients with early-stage nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys 74 (4): 1070-6, 2009.

Stage II Nasopharyngeal Cancer

Standard treatment options:

1. Chemoradiation therapy followed by adjuvant chemotherapy, as was used in the INT-0099 trial, for example.[1][Level of evidence: 3iiiA] (Patients with parapharyngeal extension were originally staged as T3 in the INT-0099 study and are now considered T2 in the current staging.)
2. High-dose radiation therapy to the primary tumor site and prophylactic radiation therapy to the nodal drainage.[2]

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage II nasopharyngeal cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

1. Cheng SH, Tsai SY, Yen KL, et al.: Concomitant radiotherapy and chemotherapy for early-stage nasopharyngeal carcinoma. J Clin Oncol 18 (10): 2040-5, 2000.
2. Xiao WW, Han F, Lu TX, et al.: Treatment outcomes after radiotherapy alone for patients with early-stage nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys 74 (4): 1070-6, 2009.

Stage III Nasopharyngeal Cancer

Standard treatment options:

1. Combined chemoradiation therapy.[1,2]
2. Combined chemoradiation therapy followed by adjuvant chemotherapy, as evidenced in INT-0099, for example.[3,4,2,5,6,7,8,9,10,11,12,13,14]
3. Altered fractionation radiation therapy.[15,16]
4. Neck dissection may be indicated for persistent or recurrent nodes if the primary tumor site is controlled.[17]

Treatment options under clinical evaluation:

  • Neoadjuvant chemotherapy. Neoadjuvant chemotherapy as given in clinical trials has been used to shrink tumors, which renders them more definitively treatable with radiation therapy. Chemotherapy is given prior to the other modalities, hence the designation neoadjuvant to distinguish it from standard adjuvant therapy, which is given after or during definitive therapy with radiation or after surgery. Many drug combinations have been used in neoadjuvant chemotherapy.

    Two randomized prospective trials compared combination chemotherapy (i.e., cisplatin, epirubicin, and bleomycin or cisplatin plus fluorouracil [5-FU] infusion) plus radiation therapy to radiation therapy alone.[3][Level of evidence: 1iiA];[18][Level of evidence: 1iiDii] Although disease-free survival was improved in the chemotherapy group for both groups, improvement in overall survival was reported only from the Intergroup trial in which chemotherapy with cisplatin was ever concurrently given.[3]

Clinical trials for advanced tumors evaluating the use of chemotherapy before radiation therapy, concomitant with radiation therapy, or as adjuvant therapy after radiation therapy should be considered.[19,20,21,22]

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage III nasopharyngeal cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

1. Langendijk JA, Leemans ChR, Buter J, et al.: The additional value of chemotherapy to radiotherapy in locally advanced nasopharyngeal carcinoma: a meta-analysis of the published literature. J Clin Oncol 22 (22): 4604-12, 2004.
2. Huncharek M, Kupelnick B: Combined chemoradiation versus radiation therapy alone in locally advanced nasopharyngeal carcinoma: results of a meta-analysis of 1,528 patients from six randomized trials. Am J Clin Oncol 25 (3): 219-23, 2002.
3. 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 16 (4): 1310-7, 1998.
4. Teo PM, Chan AT, Lee WY, et al.: Enhancement of local control in locally advanced node-positive nasopharyngeal carcinoma by adjunctive chemotherapy. Int J Radiat Oncol Biol Phys 43 (2): 261-71, 1999.
5. Chan AT, Teo PM, Ngan RK, et al.: Concurrent chemotherapy-radiotherapy compared with radiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: progression-free survival analysis of a phase III randomized trial. J Clin Oncol 20 (8): 2038-44, 2002.
6. Chua DT, Ma J, Sham JS, et al.: Long-term survival after cisplatin-based induction chemotherapy and radiotherapy for nasopharyngeal carcinoma: a pooled data analysis of two phase III trials. J Clin Oncol 23 (6): 1118-24, 2005.
7. 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 23 (27): 6730-8, 2005.
8. Zhang L, Zhao C, Peng PJ, et al.: Phase III study comparing standard radiotherapy with or without weekly oxaliplatin in treatment of locoregionally advanced nasopharyngeal carcinoma: preliminary results. J Clin Oncol 23 (33): 8461-8, 2005.
9. Baujat B, Audry H, Bourhis J, et al.: Chemotherapy in locally advanced nasopharyngeal carcinoma: an individual patient data meta-analysis of eight randomized trials and 1753 patients. Int J Radiat Oncol Biol Phys 64 (1): 47-56, 2006.
10. Baujat B, Audry H, Bourhis J, et al.: Chemotherapy as an adjunct to radiotherapy in locally advanced nasopharyngeal carcinoma. Cochrane Database Syst Rev (4): CD004329, 2006.
11. Chen Y, Liu MZ, Liang SB, et al.: Preliminary results of a prospective randomized trial comparing concurrent chemoradiotherapy plus adjuvant chemotherapy with radiotherapy alone in patients with locoregionally advanced nasopharyngeal carcinoma in endemic regions of china. Int J Radiat Oncol Biol Phys 71 (5): 1356-64, 2008.
12. Lee AW, Tung SY, Chua DT, et al.: Randomized trial of radiotherapy plus concurrent-adjuvant chemotherapy vs radiotherapy alone for regionally advanced nasopharyngeal carcinoma. J Natl Cancer Inst 102 (15): 1188-98, 2010.
13. Lee AW, Tung SY, Chan AT, et al.: A randomized trial on addition of concurrent-adjuvant chemotherapy and/or accelerated fractionation for locally-advanced nasopharyngeal carcinoma. Radiother Oncol 98 (1): 15-22, 2011.
14. Lee AW, Tung SY, Ngan RK, et al.: Factors contributing to the efficacy of concurrent-adjuvant chemotherapy for locoregionally advanced nasopharyngeal carcinoma: combined analyses of NPC-9901 and NPC-9902 Trials. Eur J Cancer 47 (5): 656-66, 2011.
15. Johnson CR, Schmidt-Ullrich RK, Wazer DE: Concomitant boost technique using accelerated superfractionated radiation therapy for advanced squamous cell carcinoma of the head and neck. Cancer 69 (11): 2749-54, 1992.
16. Chen CY, Han F, Zhao C, et al.: Treatment results and late complications of 556 patients with locally advanced nasopharyngeal carcinoma treated with radiotherapy alone. Br J Radiol 82 (978): 452-8, 2009.
17. Mendenhall WM, Werning JW, Pfister DG: Treatment of head and neck cancer. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2011, pp 729-80.
18. Preliminary results of a randomized trial comparing neoadjuvant chemotherapy (cisplatin, epirubicin, bleomycin) plus radiotherapy vs. radiotherapy alone in stage IV(> or = N2, M0) undifferentiated nasopharyngeal carcinoma: a positive effect on progression-free survival. International Nasopharynx Cancer Study Group. VUMCA I trial. Int J Radiat Oncol Biol Phys 35 (3): 463-9, 1996.
19. Azli N, Armand JP, Rahal M, et al.: Alternating chemo-radiotherapy with cisplatin and 5-fluorouracil plus bleomycin by continuous infusion for locally advanced undifferentiated carcinoma nasopharyngeal type. Eur J Cancer 28A (11): 1792-7, 1992.
20. Chan AT, Teo PM, Leung TW, et al.: A prospective randomized study of chemotherapy adjunctive to definitive radiotherapy in advanced nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys 33 (3): 569-77, 1995.
21. Merlano M, Benasso M, Corvò R, et al.: Five-year update of a randomized trial of alternating radiotherapy and chemotherapy compared with radiotherapy alone in treatment of unresectable squamous cell carcinoma of the head and neck. J Natl Cancer Inst 88 (9): 583-9, 1996.
22. Jeremic B, Shibamoto Y, Milicic B, et al.: Hyperfractionated radiation therapy with or without concurrent low-dose daily cisplatin in locally advanced squamous cell carcinoma of the head and neck: a prospective randomized trial. J Clin Oncol 18 (7): 1458-64, 2000.

Stage IV Nasopharyngeal Cancer

Standard treatment options:

1. Chemoradiation therapy followed by adjuvant chemotherapy, as evidenced in INT-0099, for example.[1,2,3,4,5,6,7,8,9,10,11,12,13,14]
2. Altered fractionation including hyperfractionated radiation therapy.[15,16]
3. Neck dissection should be reserved for persistent or recurrent nodes.[17]
4. Chemotherapy for patients with stage IVC disease.[18]

Treatment options under clinical evaluation:

1. Neoadjuvant chemotherapy. Neoadjuvant chemotherapy has been used to shrink tumors, which renders them more definitively treatable with radiation therapy. Chemotherapy is given prior to the other modalities, hence the designation neoadjuvant to distinguish it from standard adjuvant therapy, which is given after or during definitive therapy with radiation or after surgery. Many drug combinations have been used in neoadjuvant chemotherapy.

Clinical trials for advanced tumors to evaluate the use of chemotherapy before radiation therapy, concomitant with radiation therapy, or as adjuvant therapy after radiation therapy should be considered.[19,20,21,22]

A phase II, randomized study of 65 patients with stage III and IV nasopharyngeal carcinoma were randomly assigned to neoadjuvant docetaxel (75 mg/m2) and cisplatin (75 mg/m2) every 3 weeks for two cycles followed by cisplatin (40 mg/m2) every week versus chemoradiation alone. Rates of grade 3 or 4 neutropenia were 97% during the neoadjuvant arm with no difference in toxicities between the two groups during the chemoradiation portion of treatment. The 3-year progression-free survival for neoadjuvant docetaxel versus the control arm was 88.2% and 59.5% (hazard ratio [HR], 0.49; 95% confidence interval [CI], 0.20–1.19; P = .12). The 3-year overall survival for neoadjuvant docetaxel versus the control arm was 94.1% and 67.7% (HR, 0.24; 95% CI, 0.078–0.73; P = .012).[23][Level of evidence: 1iiDiii] These data have to be confirmed in a definitive phase III trial.

Three randomized, prospective trials compared combination chemotherapy (i.e., cisplatin, epirubicin, and bleomycin or cisplatin plus fluorouracil [5-FU] infusion) plus radiation therapy to radiation therapy alone.[1][Level of evidence: 1iiA];[24,25][Level of evidence: 1iiDii] Although disease-free survival (DFS) was improved in the chemotherapy group for both groups, improvement in overall survival (OS) was reported only from the Intergroup trial in which chemotherapy with cisplatin was ever concurrently given.[1]

2. Concurrent radiation therapy with chemotherapy. A study of 1,355 patients compared concurrent radiation therapy with carboplatin or cisplatin administered with 96-hour infusion of 5-FU monthly for three cycles.[26] The 3-year DFS rate was 63.4% for patients in the cisplatin arm and 60.9% for patients in the carboplatin arm (P = .961; HR, 0.70; 95% CI, 0.50–0.98). OS rates were 77% for patients in the cisplatin arm and 79% for patients in the carboplatin arm (P = .988; HR, 0.83; 95% CI, 0.63–1.010).[26][Level of evidence: 1iiA] Toxicity to kidneys and red blood cell count was greater in patients in the cisplatin group.

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage IV nasopharyngeal cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

1. 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 16 (4): 1310-7, 1998.
2. Teo PM, Chan AT, Lee WY, et al.: Enhancement of local control in locally advanced node-positive nasopharyngeal carcinoma by adjunctive chemotherapy. Int J Radiat Oncol Biol Phys 43 (2): 261-71, 1999.
3. Chan AT, Teo PM, Ngan RK, et al.: Concurrent chemotherapy-radiotherapy compared with radiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: progression-free survival analysis of a phase III randomized trial. J Clin Oncol 20 (8): 2038-44, 2002.
4. Huncharek M, Kupelnick B: Combined chemoradiation versus radiation therapy alone in locally advanced nasopharyngeal carcinoma: results of a meta-analysis of 1,528 patients from six randomized trials. Am J Clin Oncol 25 (3): 219-23, 2002.
5. Lin JC, Jan JS, Hsu CY, 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 (4): 631-7, 2003.
6. Chua DT, Ma J, Sham JS, et al.: Long-term survival after cisplatin-based induction chemotherapy and radiotherapy for nasopharyngeal carcinoma: a pooled data analysis of two phase III trials. J Clin Oncol 23 (6): 1118-24, 2005.
7. 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 23 (27): 6730-8, 2005.
8. Zhang L, Zhao C, Peng PJ, et al.: Phase III study comparing standard radiotherapy with or without weekly oxaliplatin in treatment of locoregionally advanced nasopharyngeal carcinoma: preliminary results. J Clin Oncol 23 (33): 8461-8, 2005.
9. Baujat B, Audry H, Bourhis J, et al.: Chemotherapy in locally advanced nasopharyngeal carcinoma: an individual patient data meta-analysis of eight randomized trials and 1753 patients. Int J Radiat Oncol Biol Phys 64 (1): 47-56, 2006.
10. Baujat B, Audry H, Bourhis J, et al.: Chemotherapy as an adjunct to radiotherapy in locally advanced nasopharyngeal carcinoma. Cochrane Database Syst Rev (4): CD004329, 2006.
11. Chen Y, Liu MZ, Liang SB, et al.: Preliminary results of a prospective randomized trial comparing concurrent chemoradiotherapy plus adjuvant chemotherapy with radiotherapy alone in patients with locoregionally advanced nasopharyngeal carcinoma in endemic regions of china. Int J Radiat Oncol Biol Phys 71 (5): 1356-64, 2008.
12. Lee AW, Tung SY, Chua DT, et al.: Randomized trial of radiotherapy plus concurrent-adjuvant chemotherapy vs radiotherapy alone for regionally advanced nasopharyngeal carcinoma. J Natl Cancer Inst 102 (15): 1188-98, 2010.
13. Lee AW, Tung SY, Chan AT, et al.: A randomized trial on addition of concurrent-adjuvant chemotherapy and/or accelerated fractionation for locally-advanced nasopharyngeal carcinoma. Radiother Oncol 98 (1): 15-22, 2011.
14. Lee AW, Tung SY, Ngan RK, et al.: Factors contributing to the efficacy of concurrent-adjuvant chemotherapy for locoregionally advanced nasopharyngeal carcinoma: combined analyses of NPC-9901 and NPC-9902 Trials. Eur J Cancer 47 (5): 656-66, 2011.
15. Johnson CR, Schmidt-Ullrich RK, Wazer DE: Concomitant boost technique using accelerated superfractionated radiation therapy for advanced squamous cell carcinoma of the head and neck. Cancer 69 (11): 2749-54, 1992.
16. Chen CY, Han F, Zhao C, et al.: Treatment results and late complications of 556 patients with locally advanced nasopharyngeal carcinoma treated with radiotherapy alone. Br J Radiol 82 (978): 452-8, 2009.
17. Mendenhall WM, Werning JW, Pfister DG: Treatment of head and neck cancer. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2011, pp 729-80.
18. Ma BB, Tannock IF, Pond GR, et al.: Chemotherapy with gemcitabine-containing regimens for locally recurrent or metastatic nasopharyngeal carcinoma. Cancer 95 (12): 2516-23, 2002.
19. Dimery IW, Peters LJ, Goepfert H, et al.: Effectiveness of combined induction chemotherapy and radiotherapy in advanced nasopharyngeal carcinoma. J Clin Oncol 11 (10): 1919-28, 1993.
20. Chan AT, Teo PM, Leung TW, et al.: A prospective randomized study of chemotherapy adjunctive to definitive radiotherapy in advanced nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys 33 (3): 569-77, 1995.
21. Merlano M, Benasso M, Corvò R, et al.: Five-year update of a randomized trial of alternating radiotherapy and chemotherapy compared with radiotherapy alone in treatment of unresectable squamous cell carcinoma of the head and neck. J Natl Cancer Inst 88 (9): 583-9, 1996.
22. Jeremic B, Shibamoto Y, Milicic B, et al.: Hyperfractionated radiation therapy with or without concurrent low-dose daily cisplatin in locally advanced squamous cell carcinoma of the head and neck: a prospective randomized trial. J Clin Oncol 18 (7): 1458-64, 2000.
23. 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 27 (2): 242-9, 2009.
24. Preliminary results of a randomized trial comparing neoadjuvant chemotherapy (cisplatin, epirubicin, bleomycin) plus radiotherapy vs. radiotherapy alone in stage IV(> or = N2, M0) undifferentiated nasopharyngeal carcinoma: a positive effect on progression-free survival. International Nasopharynx Cancer Study Group. VUMCA I trial. Int J Radiat Oncol Biol Phys 35 (3): 463-9, 1996.
25. Lee AW, Lau WH, Tung SY, 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 23 (28): 6966-75, 2005.
26. 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 43 (9): 1399-406, 2007.

Recurrent Nasopharyngeal Cancer

Standard treatment options:

1. Selected patients with local recurrence may be retreated with moderate-dose external-beam radiation therapy using intensity-modulated radiation therapy, stereotactic radiation therapy, or intracavitary or interstitial radiation to the site of recurrence.[1,2,3]
2. In highly selected patients, surgical resection of locally recurrent lesions may be considered.
3. If a patient has metastatic disease or local recurrence that is no longer amenable to surgery or radiation therapy, chemotherapy should be considered.[4,5,6]

Treatment options under clinical evaluation:

  • Clinical trials evaluating chemotherapy should be considered.
  • Stereotactic radiation for locally recurrent disease or persistence.[7,8,9][Level of evidence: 3iiiDiv]

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with recurrent nasopharyngeal cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

1. Mendenhall WM, Werning JW, Pfister DG: Treatment of head and neck cancer. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2011, pp 729-80.
2. Vikram B, Strong EW, Shah JP, et al.: Intraoperative radiotherapy in patients with recurrent head and neck cancer. Am J Surg 150 (4): 485-7, 1985.
3. Koutcher L, Lee N, Zelefsky M, et al.: Reirradiation of locally recurrent nasopharynx cancer with external beam radiotherapy with or without brachytherapy. Int J Radiat Oncol Biol Phys 76 (1): 130-7, 2010.
4. Al-Sarraf M: Head and neck cancer: chemotherapy concepts. Semin Oncol 15 (1): 70-85, 1988.
5. Jacobs C, Lyman G, Velez-García 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 10 (2): 257-63, 1992.
6. Foo KF, Tan EH, Leong SS, et al.: Gemcitabine in metastatic nasopharyngeal carcinoma of the undifferentiated type. Ann Oncol 13 (1): 150-6, 2002.
7. Chua DT, Sham JS, Kwong PW, et al.: Linear accelerator-based stereotactic radiosurgery for limited, locally persistent, and recurrent nasopharyngeal carcinoma: efficacy and complications. Int J Radiat Oncol Biol Phys 56 (1): 177-83, 2003.
8. Pai PC, Chuang CC, Wei KC, et al.: Stereotactic radiosurgery for locally recurrent nasopharyngeal carcinoma. Head Neck 24 (8): 748-53, 2002.
9. Xiao J, Xu G, Miao Y: Fractionated stereotactic radiosurgery for 50 patients with recurrent or residual nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys 51 (1): 164-70, 2001.

Changes to This Summary (10 / 12 / 2012)

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

Editorial changes were made to this summary.

This summary is written and maintained by the PDQ Adult Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ NCI's Comprehensive Cancer Database pages.

About This PDQ Summary

Purpose of This Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of nasopharyngeal cancer. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.

Reviewers and Updates

This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).

Board members review recently published articles each month to determine whether an article should:

  • be discussed at a meeting,
  • be cited with text, or
  • replace or update an existing article that is already cited.

Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.

The lead reviewers for Nasopharyngeal Cancer Treatment are:

  • James P. Neifeld, MD (Medical College of Virginia Hospital & Virginia Commonwealth University)
  • Minh Tam Truong, MD (Boston University Medical Center)

Any comments or questions about the summary content should be submitted to Cancer.gov through the Web site's Contact Form. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.

Levels of Evidence

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The preferred citation for this PDQ summary is:

National Cancer Institute: PDQ® Nasopharyngeal Cancer Treatment. Bethesda, MD: National Cancer Institute. Date last modified <MM/DD/YYYY>. Available at: http://cancer.gov/cancertopics/pdq/treatment/nasopharyngeal/HealthProfessional. Accessed <MM/DD/YYYY>.

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