Regionally advanced nasopharyngeal carcinoma: Long-term outcome after sequential chemotherapy and radiotherapy

Aims and background: To evaluate the long-term clinical outcome of 61 patients with regionally advanced nasopharyngeal carcinoma treated with sequential chemotherapy and radiotherapy within a phase II trial. Methods: The trial evaluated a combined modality regimen including 3 cycles of induction polychemotherapy (epirubicin 70 mg/m2 d1, and cisplatin 100 mg/m 2 d1, both recycled every 3 weeks) followed by definitive radiotherapy to the primary site (64-70 Gy) and the neck (50-70 Gy). Patients included in the trial had pathologically confirmed nasopharyngeal carcinoma; stage (UICC 1987) T-any, N2-3, MO; ECOG performance status 0-1. Sixty-one patients were enrolled between 1990 and 1996; stage according to UICC 1997 was IIb in 8%, III in 36% and IV in 56% of the patients; histology was WHO type 1-2 in 11% and WHO type 3 in 89% of cases. Minimum follow-up of 33 surviving patients is 5.2 years. Results: Clinical failure has been observed in 30 patients (49%): initial failure, observed within the third year of follow-up in all but one case, was local alone in 6 (20%), regional alone in 10 (33%), local and regional in 1 (3%), regional and distant in 1 (3%), and distant alone in 12 patients (40%). Seven patients received salvage surgery to the neck, 2 of them still disease-free at 10 and 11 years from salvage surgery; 4 patients with an isolated local relapse were re-irradiated, and one of them was alive and well at 6.5 years from salvage radiation. At 5-year local control, regional control and distant metastasis-free rates were 83%, 74% and 73%, respectively; overall and disease-free survival were 64% and 51%. Late effects of initial treatment, as evaluated in 30 patients surviving 5 years without relapse, were generally acceptable, but some degree of xerostomia, dental damage, trismus and hearing loss were reported by a significant proportion of patients (respectively 100%, 88%, 76% and 86%). Conclusions: In our experience, long-term clinical cure of regionally advanced nasopharyngeal carcinoma was obtained in 51% of cases treated with chemotherapy and radiotherapy. Salvage treatments (neck surgery, local re-irradiation) are worthy, as they increase the cure rate by approximately 10%, raising 5-year survival to over 60%. Late effects are significant, calling for refinements in radiation technique, better integration with chemotherapy to possibly decrease the need for higher radiation dose, and/or use of effective radioprotectants.