Long-term results of concurrent and adjuvant chemotherapy for advanced nasopharyngeal carcinoma

Abstract

Background: Preliminary results of a factorial trial investigating concurrent chemoradiation (CRT) and adjuvant chemotherapy (AC) for nasopharygngeal carcinoma (NPC) was reported in 2004 (JCO 22 (13): 2643–2653). This is a report on the long-term follow-up results of the study. Methods: Ho's stage T3 or N2 /N3 or > 4cm neck node, M0 disease were eligible. Patients were first randomized to receive CRT or RT alone and then further randomized to receive AC or no AC after completion of CRT/RT. Patients randomized to CRT received UFT (uracil and tegafur in 4:1 molar ratio) 200mg, 3 times a day, during radiotherapy. AC consisted of alternating PF (cisplatin 100mg/m2 D1 and 5FU 1g/m2 D1–3) and VBM (vincristine 2mg, bleomycin 30mg and methotrexate 150mg/m2, all on D1) for 6 cycles. The 4 treatment arms were: A. RT, B. CRT, C. RT + AC, D. CRT + AC. Patients in arms A and C were compared with those in arms B and D (i.e. RT vs. CRT) for efficacy of CRT. Patients in arms A and B were compared with those in arms C and D (i.e. no AC vs. AC) for efficacy of AC. Loco- regional control (LRC), distant metastases free survival (DMFS), failure-free survival (FFS) and disease-specific survival (DSS) were estimated with Kaplan-Meier methods and compared with log-rank test. Results: From May 1995 to October 2001, 222 patients were recruited. 3 patients were excluded from analysis. Median follow up time was 7 years. There were 55, 53, 54, 57 patients in arm A, B, C, D respectively. The 7-year LRC of the 4 arms were 64.2%, 74.8%, 78.7%, 78.8% respectively; DMFS were 71.7%, 85.8%, 65.5%, 80.4%; FFS were 51.7%, 69%, 53.2%, 64.4%; DSS were 71.7%, 75.4%, 66.1%, 81.5%. CRT significantly improved the DMFS and FFS compared with RT (p=0.014 and 0.016 respectively). There was a trend of improvement in DSS with CRT also (p=0.057). The use of AC failed to improve survival. Multivariate analysis showed CRT, T stage and N stage were significant for both FFS and DSS. Conclusions: CRT significantly improved DMFS and FFS in advanced NPC. The benefit of CRT was confirmed on long-term follow-up.