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.

PURPOSE: Our Phase II trial using bleomycin, epirubicin, and cisplatin (BEC) protocol in the treatment of loco-regionally advanced undifferentiated nasopharyngeal carcinoma (UCNT) patients has shown encouraging results with high objective response, disease-free survival, and overall survival rates. To establish the value of this BEC regimen as neoadjuvant chemotherapy, we initiated in 1989 a large international Phase III trial. It compares three cycles of BEC followed by radiotherapy to radiotherapy alone.

METHODS AND MATERIALS: From November 1989 to October 1993, 339 patients with negative metastases workup, stratified by accrual center have been randomized, 168 to radiotherapy alone and 171 to chemotherapy plus radiotherapy. All patients characteristics were well balanced in both arms. There was a quality control/data verification by specialist panel (radiology, histology, radiotherapy, chemotherapy) and external policy board expert every 60-80 patients having completed treatment.

RESULTS: With a median follow-up of 49 months (range: 23-70), despite an excess of treatment-related deaths in the neoadjuvant chemotherapy arm (8 vs. 1%), there is a significant difference in disease free survival favoring the chemotherapy arm (p < 0.01). The proportion of local and/or regional metastases was comparable in both arms. No difference in overall survival is seen but the numbers of events needed for analysis has not yet been reached.

CONCLUSIONS: BEC type neoadjuvant chemotherapy has a significant impact in the natural history of UCNT. Further follow-up is needed to establish an eventual overall survival difference.