Neoadjuvant chemotherapy plus conventional radiotherapy or accelerated hyperfractionation in stage III and IV nasopharyngeal carcinoma - A phase II study

A prospective phase II trial was initiated in previously untreated patients with locally advanced nasopharyngeal carcinoma (NPC). The goal was to achi eve improvement in locoregional control, disease-free interval and overall survival using induction chemotherapy and to compare conventional fractiona tion (CF) with an accelerated hyperfractionation (AHF) regimen. Fifty patie nts were treated (5 AJCC Stage III, 45 Stage IV) with induction chemotherap y consisting of two cycles of cisplatin and 5-fluorouracil. Patients were t hen randomized between CF and AHF therapy. A clinical response to induction chemotherapy was reported in 86% of patients prior to radiotherapy (44% co mplete response, 42% partial response). Patients with complete or major par tial responses to induction chemotherapy had a significantly better 5-year overall survival (60%) and disease-free interval (59%) than those with no r esponse or minor partial response (15% and 18%, p = 0.009 and 0.0009). Acut e radiation reactions were more pronounced in the AHF group (p = 0.0002), a nd the incidence of late normal tissue injury was more frequent (p = 0.08). At 5 years, the locoregional control rate was higher in the AHF arm (76%) than in the CF group (54%), but the difference was not significant (HR, 0.5 2; 95% CI, 0.15-2.83; p = 0.186). With a median follow-up period of 55 mont hs (range 4-120), the 5-year disease-free interval and overall survival rat es were more favorable in the AHF group than in the CF group, but the diffe rences were not significant (59% and 54% vs. 34% and 36%, respectively, HR for disease-free interval = 0.71; 95% CI, 0.27-1.88; p = 0.198 and HR for o verall survival = 0.81; 95% Cl, 0.37-1.78; p = 0.433). The overall treatmen t failure rate was 48%. Locoregional failures occurred in 12 patients (24%) and the incidence of distant metastases reached 30%. Response to induction chemotherapy is strongly predictive for locoregional control, disease-free interval and overall survival, Accelerated hyperfractionation was associat ed with high incidence of acute and late toxicity without significant impro vement in locoregional control rate. The optimal chemotherapy dose and sequ encing with radiotherapy needs to be investigated in future studies. Distan t metastases remain the main cause of treatment failure in NPC.