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

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).
• 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.
• Circulating cancer derived EBV-DNA in plasma.[6,7,8]
• Human papillomavirus/p16 testing.

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.[5,9,10]

EBV-DNA in plasma samples in endemic populations may be useful in screening for early asymptomatic nasopharyngeal cancer. In a study of 20,174 participants in China, 309 patients (1.5% of all participants, and 27.8% of those who initially tested positive) had persistently detectable EBV-DNA in plasma at baseline and follow up. Among the 309 participants, nasopharyngeal cancer was confirmed after nasal endoscopic examination, MRI, and biopsy in 34 patients (11.0%).[8]

Prognosis

Major prognostic factors adversely influencing outcome of treatment include the following:[11]

• Large tumor size.[12][Level of evidence: 3iiiA]
• A higher tumor (T) stage.
• The presence of involved neck nodes.
• High plasma/serum EBV-DNA levels before and after treatment.[13,14]

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.
• Family history.
• Smoking.
• Salted fish diet.[15]

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.
• Plasma/serum EBV DNA levels.

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 incidences of second primary malignancies are fewer than after treatment of tumors at other head and neck sites.[16]

Circulating cancer-derived EBV-DNA in plasma is an established tumor marker for nasopharyngeal cancer, with a sensitivity of 96% and a specificity of 93%.[6,7] The presence of short EBV-DNA fragments of fewer than 181 base pairs in the plasma of nasopharyngeal carcinoma patients suggests that EBV-DNA molecules are released into the circulation by apoptosis of cancer cells rather than by active viral replication.[17]

There are some nonkeratinizing nasopharyngeal carcinomas that are associated with HPV infection.[18] Differentiating HPV-related nasopharyngeal cancer requires identification of p16 immunohistochemical staining, in situ hybridization, and/or polymerase chain reaction in a similar way to how HPV-related oropharyngeal cancer is differentiated.

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. Mosby-Year Book, Inc., 1998.
6. Lo YM, Chan LY, Lo KW, et al.: Quantitative analysis of cell-free Epstein-Barr virus DNA in plasma of patients with nasopharyngeal carcinoma. Cancer Res 59 (6): 1188-91, 1999.
7. Leung SF, Zee B, Ma BB, et al.: Plasma Epstein-Barr viral deoxyribonucleic acid quantitation complements tumor-node-metastasis staging prognostication in nasopharyngeal carcinoma. J Clin Oncol 24 (34): 5414-8, 2006.
8. Chan KCA, Woo JKS, King A, et al.: Analysis of Plasma Epstein-Barr Virus DNA to Screen for Nasopharyngeal Cancer. N Engl J Med 377 (6): 513-522, 2017.
9. 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. Lippincott Williams & Wilkins, 2011, pp 729-80.
10. Laramore GE, ed.: Radiation Therapy of Head and Neck Cancer. Springer-Verlag, 1989.
11. 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.
12. 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.
13. Leung SF, Chan AT, Zee B, et al.: Pretherapy quantitative measurement of circulating Epstein-Barr virus DNA is predictive of posttherapy distant failure in patients with early-stage nasopharyngeal carcinoma of undifferentiated type. Cancer 98 (2): 288-91, 2003.
14. Chan AT, Lo YM, Zee B, et al.: Plasma Epstein-Barr virus DNA and residual disease after radiotherapy for undifferentiated nasopharyngeal carcinoma. J Natl Cancer Inst 94 (21): 1614-9, 2002.
15. Xie SH, Yu IT, Tse LA, et al.: Tobacco smoking, family history, and the risk of nasopharyngeal carcinoma: a case-referent study in Hong Kong Chinese. Cancer Causes Control 26 (6): 913-21, 2015.
16. 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.
17. Chan KC, Zhang J, Chan AT, et al.: Molecular characterization of circulating EBV DNA in the plasma of nasopharyngeal carcinoma and lymphoma patients. Cancer Res 63 (9): 2028-32, 2003.
18. Robinson M, Suh YE, Paleri V, et al.: Oncogenic human papillomavirus-associated nasopharyngeal carcinoma: an observational study of correlation with ethnicity, histological subtype and outcome in a UK population. Infect Agent Cancer 8 (1): 30, 2013.

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.

The World Health Organization (WHO) definition of nasopharyngeal carcinoma is a "carcinoma arising in the nasopharyngeal mucosa that shows light microscopic or ultrastructural evidence of squamous differentiation." The WHO classification for nasopharyngeal carcinoma has evolved over time and the 2005 classification is the current one.[1] The three versions below are all used, and in particular, the undifferentiated carcinomas that carry the worst prognosis and the greatest sensitivity to chemoradiation are generally classified according to the 1978 definitions.[2]

1978 WHO classification:

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

1991 WHO classification:

1. Squamous cell carcinoma.
2. Nonkeratinizing squamous cell carcinoma.
   • Differentiated nonkeratinizing carcinoma.
   • Undifferentiated carcinoma.

2005 WHO classification:

1. Keratinizing squamous cell carcinoma.
2. Nonkeratinizing carcinoma.
   • Differentiated nonkeratinizing carcinoma.
   • Undifferentiated carcinoma.
3. Basaloid squamous cell carcinoma.

Previous subdivisions of nasopharyngeal carcinoma included lymphoepithelioma, which is now classified as WHO grade III and characterized by lymphoid infiltrate.[3]

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 (1978) represent the endemic form of nasopharyngeal carcinoma and is found in Southern China.

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

References:

1. Thompson LD: Update on nasopharyngeal carcinoma. Head Neck Pathol 1 (1): 81-6, 2007.
2. Shanmugaratnam K, Chan SH, de-Thé G, et al.: Histopathology of nasopharyngeal carcinoma: correlations with epidemiology, survival rates and other biological characteristics. Cancer 44 (3): 1029-44, 1979.
3. Shanmugaratnam K, Sobin L: Histological Typing of Upper Respiratory Tract Tumours. World Health Organization, 1978. International Histologic Classification of Tumours: No. 19.

Stage Information for Nasopharyngeal Cancer

Staging systems are for 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 (CT) 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 targeted delineation of the primary tumor and aid in the detection of metastatic nodal involvement and metastatic spread, such as that found in 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.

Epithelial tumors of the nasopharynx are staged using this staging system.

American Joint Committee on Cancer (AJCC) Stage Groupings and TNM Definitions

The AJCC has designated staging by TNM (tumor, node, metastasis) classification to define nasopharyngeal cancer.[7]

Table 1. Definition of TNM Stage 0^a

Stage	TNM	Description
T = primary tumor; N = regional lymph node; M = distant metastasis.
a Reprinted with permission from AJCC: Nasopharynx. In: Amin MB, Edge SB, Greene FL, et al., eds.:AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp 103–11.
0	Tis, N0, M0	Tis = Carcinomain situ.
		N0 = No regional lymph node metastasis.
		M0 = No distant metastasis.

Table 2. Definition of TNM Stage I^a

Stage	TNM	Description
T = primary tumor; N = regional lymph node; M = distant metastasis.
a Reprinted with permission from AJCC: Nasopharynx. In: Amin MB, Edge SB, Greene FL, et al., eds.:AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp 103–11.
I	T1, N0, M0	T1 = Tumor confined to nasopharynx, or extension to oropharynx and/or nasal cavity without parapharyngeal involvement.
		N0 = No regional lymph node metastasis.
		M0 = No distant metastasis.

Table 3. Definition of TNM Stage II^a

Stage	TNM	Description
T = primary tumor; N = regional lymph node; M = distant metastasis.
a Reprinted with permission from AJCC: Nasopharynx. In: Amin MB, Edge SB, Greene FL, et al., eds.:AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp 103–11.
II	T0, T1, N1, M0	T0 = No tumor identified, but EBV-positive cervical node(s) involvement.
		Tis = Carcinomain situ.
		T1 = Tumor confined to nasopharynx, or extension to oropharynx and/or nasal cavity without parapharyngeal involvement.
		N1 = Unilateral metastasis in cervical lymph node(s) and/or unilateral or bilateral metastasis in retropharyngeal lymph node(s), ≤6 cm in greatest dimension, above the caudal border of cricoid cartilage.
		M0 = No distant metastasis.
	T2, N0, M0	T2 = Tumor with extension to parapharyngeal space, and/or adjacent soft tissue involvement (medial pterygoid, lateral pterygoid, prevertebral muscles).
		N0 = No regional lymph node metastasis.
		M0 = No distant metastasis.
	T2, N1, M0	T2 = Tumor with extension to parapharyngeal space, and/or adjacent soft tissue involvement (medial pterygoid, lateral pterygoid, prevertebral muscles).
		N1 = Unilateral metastasis in cervical lymph node(s) and/or unilateral or bilateral metastasis in retropharyngeal lymph node(s), ≤6 cm in greatest dimension, above the caudal border of cricoid cartilage.
		M0 = No distant metastasis.

Table 4. Definition of TNM Stage III^a

Stage	TNM	Description
T = primary tumor; N = regional lymph node; M = distant metastasis; EBV = Epstein-Barr virus.
a Reprinted with permission from AJCC: Nasopharynx. In: Amin MB, Edge SB, Greene FL, et al., eds.:AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp 103–11.
III	T0, T1, N2, M0	T0 = No tumor identified, but EBV-positive cervical node(s) involvement.
		Tis = Carcinomain situ.
		T1 = Tumor confined to nasopharynx, or extension to oropharynx and/or nasal cavity without parapharyngeal involvement.
		N2 = Bilateral metastasis in cervical lymph node(s), ≤6 cm in greatest dimension, above the caudal border of cricoid cartilage.
		M0 = No distant metastasis.
	T2, N2, M0	T2 = Tumor with extension to parapharyngeal space, and/or adjacent soft tissue involvement (medial pterygoid, lateral pterygoid, prevertebral muscles).
		N2 = Bilateral metastasis in cervical lymph node(s), ≤6 cm in greatest dimension, above the caudal border of cricoid cartilage.
		M0 = No distant metastasis.
	T3, N0, M0	T3 = Tumor with infiltration of bony structures at skull base, cervical vertebra, pterygoid structures, and/or paranasal sinuses.
		N0 = No regional lymph node metastasis.
		M0 = No distant metastasis.
	T3, N1, M0	T3 = Tumor with infiltration of bony structures at skull base, cervical vertebra, pterygoid structures, and/or paranasal sinuses.
		N1 = Unilateral metastasis in cervical lymph node(s) and/or unilateral or bilateral metastasis in retropharyngeal lymph node(s), ≤6 cm in greatest dimension, above the caudal border of cricoid cartilage.
		M0 = No distant metastasis.
	T3, N2, M0	T3 = Tumor with infiltration of bony structures at skull base, cervical vertebra, pterygoid structures, and/or paranasal sinuses.
		N2 = Bilateral metastasis in cervical lymph node(s), ≤6 cm in greatest dimension, above the caudal border of cricoid cartilage.
		M0 = No distant metastasis.

Table 5. Definition of TNM Stages IVA and IVB^a

Stage	TNM	Description
T = primary tumor; N = regional lymph node; M = distant metastasis; EBV = Epstein-Barr virus.
a Reprinted with permission from AJCC: Nasopharynx. In: Amin MB, Edge SB, Greene FL, et al., eds.:AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp 103–11.
IVA	T4, N0, M0	T4 = Tumor with intracranial extension, involvement of cranial nerves, hypopharynx, orbit, parotid gland, and/or extensive soft tissue infiltration beyond the lateral surface of the lateral pterygoid muscle.
		N0 = No regional lymph node metastasis.
		M0 = No distant metastasis.
	T4, N1, M0	T4 = Tumor with intracranial extension, involvement of cranial nerves, hypopharynx, orbit, parotid gland, and/or extensive soft tissue infiltration beyond the lateral surface of the lateral pterygoid muscle.
		N1 = Unilateral metastasis in cervical lymph node(s) and/or unilateral or bilateral metastasis in retropharyngeal lymph node(s), ≤6 cm in greatest dimension, above the caudal border of cricoid cartilage.
		M0 = No distant metastasis.
	T4, N2, M0	T4 = Tumor with intracranial extension, involvement of cranial nerves, hypopharynx, orbit, parotid gland, and/or extensive soft tissue infiltration beyond the lateral surface of the lateral pterygoid muscle.
		N2 = Bilateral metastasis in cervical lymph node(s), ≤6 cm in greatest dimension, above the caudal border of cricoid cartilage.
		M0 = No distant metastasis.
	Any T, N3, M0	TX = Primary tumor cannot be assessed.
		T0 = No tumor identified, but EBV-positive cervical node(s) involvement.
		Tis = Carcinomain situ.
		T1 = Tumor confined to nasopharynx, or extension to oropharynx and/or nasal cavity without parapharyngeal involvement.
		T2 = Tumor with extension to parapharyngeal space, and/or adjacent soft tissue involvement (medial pterygoid, lateral pterygoid, prevertebral muscles).
		T3 = Tumor with infiltration of bony structures at skull base, cervical vertebra, pterygoid structures, and/or paranasal sinuses.
		T4 = Tumor with intracranial extension, involvement of cranial nerves, hypopharynx, orbit, parotid gland, and/or extensive soft tissue infiltration beyond the lateral surface of the lateral pterygoid muscle.
		N3 = Unilateral or bilateral metastasis in cervical lymph node(s), >6 cm in greatest dimension, and/or extension below the caudal border of cricoid cartilage.
		M0 = No distant metastasis.
IVB	Any T, Any N, M1	Any T = See Stage IVA above.
		NX = Regional lymph nodes cannot be assessed.
		N0 = No regional lymph node metastasis.
		N1 = Unilateral metastasis in cervical lymph node(s) and/or unilateral or bilateral metastasis in retropharyngeal lymph node(s), ≤6 cm in greatest dimension, above the caudal border of cricoid cartilage.
		N2 = Bilateral metastasis in cervical lymph node(s), ≤6 cm in greatest dimension, above the caudal border of cricoid cartilage.
		N3 = Unilateral or bilateral metastasis in cervical lymph node(s), >6 cm in greatest dimension, and/or extension below the caudal border of cricoid cartilage.
		M1 = Distant metastasis.

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. Lippincott Williams & Wilkins, 2011, pp 729-80.
4. Laramore GE, ed.: Radiation Therapy of Head and Neck Cancer. 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. Nasopharynx. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. Springer; 2017, pp. 103–11.

Treatment Option Overview

Standard treatments for patients with nasopharyngeal cancer include the following:

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

High-dose radiation therapy with chemotherapy is the primary treatment of nasopharyngeal cancer 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 Radiation Therapy Oncology Group (RTOG) study (RTOG-0225) showed the feasibility of IMRT in a multi-institutional setting and minimal grade 3 and 4 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 before 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 website.

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. 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, 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 for Stage I Nasopharyngeal Cancer

Standard treatment options for stage I nasopharyngeal cancer:

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

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

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 for Stage II Nasopharyngeal Cancer

Standard treatment options for stage II nasopharyngeal cancer:

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

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

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 for Stage III Nasopharyngeal Cancer

Standard treatment options for stage III nasopharyngeal cancer:

1. Combined chemoradiation therapy.[1,2]
2. Combined chemoradiation therapy followed by adjuvant chemotherapy.[2,3,4,5,6,7,8,9,10,11,12,13,14,15]
3. Altered fractionation radiation therapy.[16,17]
4. Neck dissection may be indicated for persistent or recurrent nodes if the primary tumor site is controlled.[18]

Treatment Options Under Clinical Evaluation for Stage III Nasopharyngeal Cancer

Treatment options under clinical evaluation for stage III nasopharyngeal cancer:

• 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 administered before the other modalities; therefore, the designation neoadjuvant is used 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 infusion) plus radiation therapy with radiation therapy alone.[3][Level of evidence: 1iiA];[19][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 concurrently given.[3]

Clinical trials for advanced tumors evaluating the use of chemotherapy before radiation therapy, concurrent with radiation therapy, or as adjuvant therapy after radiation therapy should be considered.[20,21,22,23]

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

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. Zhang Y, Chen L, Hu GQ, et al.: Gemcitabine and Cisplatin Induction Chemotherapy in Nasopharyngeal Carcinoma. N Engl J Med 381 (12): 1124-1135, 2019.
16. 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.
17. 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.
18. 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. Lippincott Williams & Wilkins, 2011, pp 729-80.
19. 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.
20. 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.
21. 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.
22. 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.
23. 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 for Stage IV Nasopharyngeal Cancer

Standard treatment options for stage IV nasopharyngeal cancer:

1. Chemoradiation therapy followed by adjuvant chemotherapy.[1,2,3,4,5,6,7,8,9,10,11,12,13,14,15]
2. Altered fractionation including hyperfractionated radiation therapy.[16,17]
3. Neck dissection should be reserved for persistent or recurrent nodes.[18]
4. Chemotherapy for patients with stage IVC disease.[19]

Treatment Options Under Clinical Evaluation for Stage IV Nasopharyngeal Cancer

Treatment options under clinical evaluation for stage IV nasopharyngeal cancer:

1. Neoadjuvant chemotherapy. Neoadjuvant chemotherapy has been used to shrink tumors, which renders them more definitively treatable with radiation therapy. Chemotherapy is administered before the other modalities; therefore 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, concurrent with radiation therapy, or as adjuvant therapy after radiation therapy should be considered.[20,21,22,23]

   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 (OS) for neoadjuvant docetaxel was 94.1% compared with the control arm, which was 67.7% (HR, 0.24; 95% CI, 0.078–0.73; P = .012).[24][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 with radiation therapy alone.[1][Level of evidence: 1iiA]; [25,26][Level of evidence: 1iiDii] Although disease-free survival (DFS) was improved in the chemotherapy group for both groups, improvement in OS was reported only from the Intergroup trial in which chemotherapy with cisplatin was 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.[27] 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).[27][Level of evidence: 1iiA] Toxicity to kidneys and red blood cell count was greater in patients in the cisplatin group.

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

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. Zhang Y, Chen L, Hu GQ, et al.: Gemcitabine and Cisplatin Induction Chemotherapy in Nasopharyngeal Carcinoma. N Engl J Med 381 (12): 1124-1135, 2019.
16. 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.
17. 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.
18. 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. Lippincott Williams & Wilkins, 2011, pp 729-80.
19. 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.
20. 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.
21. 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.
22. 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.
23. 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.
24. 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.
25. 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.
26. 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.
27. 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 for Recurrent Nasopharyngeal Cancer

Standard treatment options for recurrent nasopharyngeal cancer:

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]

Chemotherapy

Evidence (chemotherapy):

1. In a multicenter, randomized, open-label phase III trial, patients with recurrent or metastatic nasopharyngeal carcinoma recruited from 22 hospitals in China, were randomly assigned in a 1:1 ratio to receive either gemcitabine (1 g/m² intravenously (IV) on days 1 and 8) and cisplatin (80 mg/m² IV on day 1), or fluorouracil ([5-FU] 4 g/m² in continuous IV infusion over 96 h) and cisplatin (80 mg/m² IV on day 1) once every 3 weeks for a maximum of six cycles.[7][Level of evidence: 1iiDiii] Of the 362 patients, 181 were assigned to the gemcitabine plus cisplatin group and 181 to the 5-FU plus cisplatin group.
   • Median follow-up time for progression-free survival (PFS) was 19.4 months (interquartile range [IQR], 12.1–35.6). The median PFS was 7.0 months (4.4–10.9) in the gemcitabine group and 5.6 months (3.0–7.0) in the 5-FU group (hazard ratio [HR] 0.55 [95% confidence interval [CI], 0.44–0.68]; P < .0001).
   • Significantly different treatment-related grade 3 or 4 adverse events between the gemcitabine and 5-FU groups were leucopenia (52 [29%] vs. 15 [9%]; P < .0001), neutropenia (41 [23%] vs. 23 [13%]; P = . 0251), thrombocytopenia (24 [13%] vs. 3 [2%]; P = .0007), and mucosal inflammation (0 vs. 25 [14%]; P < .0001).
   • Serious treatment-related adverse events occurred in seven (4%) patients in the gemcitabine group and ten (6%) in the 5-FU group. Six (3%) patients in the gemcitabine group and 14 (8%) patients in the 5-FU group discontinued treatment because of drug-related adverse events.
   • No treatment-related deaths occurred in either group.

Treatment Options Under Clinical Evaluation for Recurrent Nasopharyngeal Cancer

Treatment options under clinical evaluation for recurrent nasopharyngeal cancer:

• Clinical trials evaluating chemotherapy should be considered.
• Stereotactic radiation for locally recurrent disease or persistence.[8,9,10][Level of evidence: 3iiiDiv]

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

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. 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. 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 388 (10054): 1883-1892, 2016.
8. 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.
9. Pai PC, Chuang CC, Wei KC, et al.: Stereotactic radiosurgery for locally recurrent nasopharyngeal carcinoma. Head Neck 24 (8): 748-53, 2002.
10. 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 (08 / 30 / 2019)

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.

Stage III Nasopharyngeal Cancer

Added Zhang et al. as reference 15.

Stage IV Nasopharyngeal Cancer

Added Zhang et al. as reference 15.

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 adult nasopharyngeal cancer. It is intended as a resource to inform and assist clinicians in the care of their 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 (Adult) are:

• Ann W. Gramza, MD (Georgetown Lombardi Comprehensive Cancer Center)
• Minh Tam Truong, MD (Boston University Medical Center)

Any comments or questions about the summary content should be submitted to Cancer.gov through the NCI website's Email Us. 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

Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Adult Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.

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PDQ is a registered trademark. Although the content of PDQ documents can be used freely as text, it cannot be identified as an NCI PDQ cancer information summary unless it is presented in its entirety and is regularly updated. However, an author would be permitted to write a sentence such as "NCI's PDQ cancer information summary about breast cancer prevention states the risks succinctly: [include excerpt from the summary]."

The preferred citation for this PDQ summary is:

PDQ® Adult Treatment Editorial Board. PDQ Nasopharyngeal Cancer Treatment (Adult). Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/types/head-and-neck/hp/adult/nasopharyngeal-treatment-pdq. Accessed <MM/DD/YYYY>. [PMID: 26389193]

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Last Revised: 2019-08-30