A PROSPECTIVE RANDOMIZED STUDY OF CHEMOTHERAPY ADJUNCTIVE TO DEFINITIVE RADIOTHERAPY IN ADVANCED NASOPHARYNGEAL CARCINOMA

Purpose: A prospective randomized trial was conducted to compare chemo radiotherapy against radiotherapy alone in the treatment of locoregion ally advanced nasopharyngeal carcinoma. Methods and Materials: Eighty- two patients with histologically proven nasopharyngeal carcinoma who h ad either Ho's N3 staging or any N stage with a nodal diameter of grea ter than or equal to 4 cm were entered. Seventy-seven patients were ev aluable for tumor response and survival. The patients were randomized to receive two cycles of cisplatin 100 mg/m(2) Day 1, 5-fluorouracil 1 000 mg/m(2) 24-h infusion Days 2, 3, and 4 before radical radiotherapy , and four cycles of postradiotherapy chemotherapy (37 patients) or ra diotherapy alone (40 patients). All patients received radical radiothe rapy to the nasopharynx and neck. The nasopharynx and upper neck were treated to 66 Gy by conventional fractionation and the lower neck to 5 8 Gy. Booster radiotherapy (7.5 Gy/two fractions/week) was given to an y residual nodes after standard radiotherapy. Results: The patient cha racteristics, including staging, were similar in both arms. The overal l response rate to neoadjuvant chemotherapy was 81% (19% complete resp onse, 62% partial response). The rates of radiotherapy for boosting pa rapharyngeal disease or residual lymph nodes were not significantly di fferent in the two arms. The overall complete response rate to chemora diotherapy was 100%, and to radiotherapy alone, 95%. Toxicities in the chemoradiotherapy arm were mainly myelosuppression, nephrotoxicity, a nd nausea and vomiting. The degree of mucositis was not significantly different in the two arms. There was no treatment-related death. The m edian follow up was 28.5 months. The 2-year overall survival was 80% i n the chemoradiotherapy arm and 80.5% in the radiotherapy arm. The 2-y ear disease-free survival was 68% in the chemoradiotherapy arm and 72% in the radiotherapy arm, without significant difference between the t wo arms. The locoregional relapse rate, distant metastatic rate, and m edian time to relapse were also not significantly different between th e two arms. Conclusion: Despite promising tumor response rates from Ph ase II trials, this prospective randomized trial has demonstrated no b enefit from adjunctive chemotherapy to radiotherapy in the treatment o f locoregionally advanced nasopharyngeal carcinoma.