Carcinoma of the nasopharynx is uncommon in the United States. Among H&N cancers, it has among the highest propensity to metastasize to distant sites. Nasopharyngeal cancer also poses a significant risk for isolated local recurrences after definitive radiation (without chemotherapy) for locally advanced disease.244-247 Regional recurrences are uncommon in this disease, occurring in only 10% to 19% of patients.247,248 The NCCN Guidelines for the evaluation and management of carcinoma of the nasopharynx attempt to address risk for both local and distant disease. Stage is accepted as prognostically important. The prognostic significance of histology is still controversial. RT was the standard treatment for all stages of this disease, until the mid-1990s, when trial data showed improved survival for locally advanced tumors treated with concurrent RT and cisplatin.239 In 2013, extensive revisions were made to the radiation guidelines (see
Principles of Radiology in the NCCN Guidelines for Cancer of the
Nasopharynx; see also Head and Neck Radiation Therapy in this Discussion).
Workup and Staging
The workup of nasopharyngeal cancer includes a complete H&N examination and other studies; it was revised in 2013 for clarification (see the NCCN Guidelines for Cancer of the Nasopharynx). These studies are important to determine the full extent of tumor in order to assign stage appropriately and to design radiation ports that will encompass all the disease with appropriate doses. Multidisciplinary consultation is encouraged. The 2010 AJCC staging classification (7th edition) is used as the basis for treatment recommendations (see Table 2).16
Treatment
Patients with T1, N0, M0 nasopharyngeal tumors may be treated with definitive RT alone (see the NCCN Guidelines for Cancer of the
Nasopharynx). For early-stage cancer in this setting, radiation doses of 66 to 70 Gy given with standard fractions are necessary for control of the primary tumor and involved lymph nodes (see Principles of
Radiation Therapy in the NCCN Guidelines for Cancer of the
Nasopharynx). The local control rate for these tumors ranges from 80% to 90%, whereas T3–4 tumors have a control rate of 30% to 65% with RT alone.249,250
The combination of RT and concurrent platinum-based chemotherapy followed by adjuvant cisplatin/5-FU has been shown to increase the local control rate from 54% to 78%. The Intergroup trial 0099, which randomly assigned patients to chemotherapy plus external-beam RT versus external radiation alone, closed early when an interim analysis disclosed a significant survival advantage favoring the combined chemotherapy and radiation group.239 The addition of chemotherapy also decreased local, regional, and distant recurrence rates.
A similar randomized study conducted in Singapore, which was
modeled after the Intergroup treatment regimen, continued to show the benefit of adding chemotherapy to RT. After combined chemotherapy and radiation, adjuvant chemotherapy was also given in this trial.251 In addition, the administration of the cisplatin dose was spread out over several days, and this regimen appeared to reduce toxicity while still providing a beneficial antitumor effect.
Another phase III randomized trial showed that concurrent
chemotherapy/RT (using weekly cisplatin) increased survival when compared with RT alone.252 Five-year overall survival was 70% for the chemotherapy/RT group versus 59% for the RT group. A randomized
trial compared chemotherapy/RT using cisplatin versus carboplatin and found that the 3-year overall survival rates were similar (78% vs.
79%).237 However, the NCCN Guidelines recommend cisplatin for chemotherapy/RT in patients who do not have a contraindication to the drug, because more randomized data support the use of cisplatin in this setting (see Principles of Systemic Therapy in the NCCN Guidelines for Head and Neck Cancers).239,252 A recent phase III randomized trial compared concurrent chemotherapy/RT with (or without) adjuvant chemotherapy (cisplatin/5-FU).253 The addition of adjuvant
chemotherapy did not lead to a significant improvement in the reported outcomes including overall survival, although long-term survival data are not yet available.
The NCCN Guidelines recommend concurrent chemotherapy (cisplatin) plus RT followed by adjuvant cisplatin/5-FU (category 1 for the entire regimen) for both T1, N1–3; and for T2–T4, any N lesions (see the NCCN Guidelines for Cancer of the Nasopharynx).239,252 Adjuvant carboplatin/5-FU is also an option (see Principles of Systemic Therapy in the NCCN Guidelines for Head and Neck Cancers).254 Concurrent chemotherapy/RT alone is also listed as an option (category 2B) for these patients. The panel is interested in further follow-up to the Chen et al study to clarify the role of adjuvant chemotherapy in this setting.253 Induction chemotherapy (category 3) (followed by chemotherapy/RT) is also recommended for patients with nasopharyngeal cancer with either T1, N1–3 or T2–T4, any N lesions (see the NCCN Guidelines for Cancer of the Nasopharynx). Panel members had widespread
disagreement regarding whether induction chemotherapy is appropriate, which is reflected in the category 3 recommendation (see The Induction
Chemotherapy Controversy in this Discussion). Several
induction/sequential chemotherapy options are recommended in the algorithm for nasopharyngeal cancer (see Principles of Systemic
Therapy in the NCCN Guidelines for Head and Neck
Cancers).205,237,252,255 Although an unusual occurrence, a patient with residual disease in the neck and a complete response at the primary should undergo a neck dissection.
For patients who present with metastatic disease, recommended initial therapy includes either a platinum-based combination chemotherapy regimen or concurrent chemotherapy/RT; treatment depends on whether disease is localized or widespread (see NCCN Guidelines for Cancer of the Nasopharynx).239,252,254 For platinum-based combination chemotherapy, the different options are listed in the algorithm (see
Principles of Systemic Therapy in the NCCN Guidelines for Head and
Neck Cancers).237,255
The management of patients with recurrent or persistent
nasopharyngeal cancer is described in the algorithm (see NCCN
Guidelines for Cancer of the Nasopharynx). Unless otherwise specified, regimens or single agents can be used for either nasopharyngeal or non-nasopharyngeal cancer (see Principles of Systemic Therapy in the NCCN Guidelines for Head and Neck Cancers). Combination therapy options include: 1) cisplatin or carboplatin with docetaxel or paclitaxel; 2) cisplatin/5-FU; or 3) cetuximab/carboplatin.256 For those who have failed platinum-based therapy, options are listed in the algorithm (see
Principles of Systemic Therapy in the NCCN Guidelines for Head and
Neck Cancers).257,258 Follow-up/Surveillance
Recommendations for surveillance are provided in the algorithm (see
Follow-up Recommendations in the NCCN Guidelines for Head and
Version 2.2013, 05/29/13 © National Comprehensive Cancer Network, Inc. 2013, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®. MS-24
Discussion