Final results of a phase III randomized study of concurrent weekly cisplatin-RT versus RT alone in locoregionally advanced nasopharyngeal carcinoma (NPC)

Abstract
5523 Background/Objective: NPC is highly radiosensitive and chemosensitive. 3 cycles of 3-weekly chemotherapy concurrent with RT followed by 3 cycles of adjuvant chemotherapy has improved survival over RT alone in a previous randomized study. The regimen was associated with significant toxicities. This randomized phase III study compared concurrent weekly cisplatin-RT with RT alone in patients with locoregionally advanced NPC. Methods: Patients with Ho's N2 or N3 stage or N1 stage with nodal size ≥ 4 cm were randomized to receive cisplatin 40 mg/m2 weekly up to 8 weeks concurrently with RT (CRT) or RT alone. The primary endpoints are progression-free survival (PFS) and overall survival (OS). Results: 350 eligible patients were randomized. Baseline patient characteristics, treatment toxicities and PFS analysis at median follow up of 2.71 years have been published previously. At a median follow up of 5.5 years where 58 and 73 deaths were found out of 174 CRT and 176 RT patients respectively (95th and 5th percentiles ranging from 3.8 to 8.7 years respectively), the 5 year PFS was 62% for the CRT arm and 52% for the RT arm (p=0.0764 with a hazards ratio of 1.33 and a 95% C.I. 0.97 to 1.84). The 5 year OS was 72% for the CRT arm and 59% for the RT arm (p=0.0479) with a hazards ratio of 1.41 (95% C.I. 1.00 to 2.00). Using Cox regression analysis, male sex (p=0.0284), advanced Ho's T (p=0.0002) and advanced age (p=0.0019) had poorer prognoses. The treatment-by-covariate interaction effect was not significant under the Cox model (p=0.1122, 3 d.f.). The treatment effect on OS remains borderline significant in favor of CRT (p=0.0586, with hazards ratio of 1.40 with 95% C.I. 0.99 to 1.97) after adjusting for significant covariates. There were no treatment-related deaths. In the CRT arm, 4.6% of patients had grade 4 mucositis and 12.6% of patients had grade 3 leukopenia. Conclusion: Weekly cisplatin-RT is well tolerated in patients with advanced NPC in endemic areas and is associated with clinically significant improvement in PFS and OS. This regime can be offered as standard treatment in locoregionally advanced NPC. No significant financial relationships to disclose.