Nasopharyngeal Cancer

Nasopharyngeal cancer is a highly radioresponsive tumor. This is especially true for the World Health Organization (WHO) class II and III (nonkeratinizing and undifferentiated squamous cell carcinoma). In the United States, however, 30 to 50% of patients will have WHO class I (keratinized squamous cell carcinoma), which is associated with alcohol and tobacco use and is much less radiosensitive.77 Advanced-stage disease is associated with poor 5-year survival rates, within a range of 10 to 40% when treatment is with radiotherapy alone. For this reason, adding chemotherapy to the treatment protocol has been investigated.

Several trials have evaluated the use of neoadjuvant chemotherapy in this disease. In a noncontrolled study from Israel, 27 patients treated with induction cisplatin and 5-FU achieved a 93% response rate (37% CR).78 The 5 -year actuarial survival was 66%. Again, those patients achieving a CR did significantly better, with all patients in this subgroup alive at the end of the follow-up period. Investigators from M.D. Anderson reported on a randomized trial comparing neoadjuvant cisplatin and 5-FU with radiation alone. This study showed a significantly improved 5-year survival rate in the neoadjuvant group, 69 to 48%. Another trial used neoadjuvant and adjuvant treatment, both using cisplatin and 5-FU. In this study, all patients were WHO stage III. No significant difference was found in either the 2-year disease-free survival or the overall survival rates.

A landmark article was reported by Al-Sarraf for the Inter-group Study 0099. This trial reported on 147 patients randomized to receive either 70 gray (Gy) of external beam radiation or the same radiation treatment with the addition of three doses of concomitant cisplatin (100 mg/m2) and three courses of adjuvant treatment with cisplatin and 5-FU. The patients had stage III and IV disease and were stratified by tumor and nodal stage, WHO histologic category, and performance status. The trial was closed before accrual of the pre-specified 270 patients, as there was a highly significant difference in the two groups at the interim analysis. The progression-free survival rates were 24% and 69%, respectively, for radiotherapy versus chemo- and radiotherapy (P < 0.001). Overall survival was also highly significant, with rates of 47% and 78%, respectively (P = 0.005). Although this treatment response may not be reflective of results achievable for groups in whom WHO type III tumors predominate, this trial has reset the standard therapy for nasopharyngeal carcinoma in the United States.

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