The nasopharynx is a cubical cavity located behind the nasal cavity and superior to the soft palate. Superiorly it borders the base of skull and floor of the sphenoid sinus.Laterally it is perforated by the eustachian tubes, which connect to internal ears. Nasopharynx is rich in lymphatics. Patients with nasopharyngeal cancer may present withenlarged neck lymph nodes even in the absence of other symptoms.
Nasopharyngeal cancer is a relatively rare disease in the United States, approximately 0.6 to 0.8 per 100,000 population. The highest prevalent is in southern China, withincidence rates as high as 20 per 100,000. The incidence for descendants of southern Chinese living in other countries remains higher than the other population.
Because of the anatomic location of nasopharyngeal cancer, surgical resection of a primary lesion is successful. Radiation therapy (XRT) is considered the treatment ofchoice for the majority of patients with this disease. However, the local control and survival of patients with loco-regionally advanced disease treated with radiation aloneremain unsatisfactory. Some Phase II trials using combination of chemotherapy (CTX) and radiation therapy have shown promising results. This led to the National Headand Neck Cancer Intergroup randomized phase III trial of advanced nasopharyngeal cancer. Southwest Oncology Group (SWOG) with participation of Radiation TherapyOncology Group (RTOG) and Eastern Cooperative Oncology Group (ECOG) coordinated this study.
Patients with histologically proven stage III and IV nasopharyngeal cancer without evidence of systemic metastasis (M0) were enrolled in this study. The patients wererandomized to 2 arms: A) XRT alone versus B) CTX concurrent with XRT. The XRT was the same for both arms, which was 1.8-2.0Gy/day for 35 to 39 fractions for atotal dose of 70Gy. The investigation arm received chemotherapy with cisplatin 100mg/m2 on days 1, 22, and 43 concurrently with XRT. CTX was continued aftercompletion of XRT, using cisplatin 80mg/m2 on day1 and fluorouracil 1,000 mg/m2/day on days 1 to 4 every 4 weeks for total of 3 courses. Chemotherapy dose wasmodified bases upon the neutrophil and platelet count and renal function.
A total of 193 patients were registered onto the study with 147 evaluable for primary analysis of survival and toxicity. Sixty-nine patients were in XRT group and 78patients in CTX/XRT group. The majority of patients had stage IV disease. The performance status was 0-1 in more than 90% of patients. The median progression-freesurvival (PFS) time for the radiotherapy group was 15 months and had not been reached for the combined group. The 3-year actuarial PFS rates were 24% and 69%,respectively (p< 0.001). The 3-year overall survival rate was 47% and 78%, respectively (p< 0.005). CTX/XRT was associated with higher incidence of grade 3 and 4 toxicity and higher percentage of non-compliance.
This study demonstrated that CTX/XRT was superior to XRT alone in preventing loco-regional recurrence and distant metastases. In addition, this is the first randomizedstudy to demonstrate an overall survival benefit with the use of concurrent CTX/XRT followed by adjuvant CTX as compared with XRT alone. More effective systemictreatment is needed to reduce the high systemic recurrences to improve the results further.
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