Five-year update on a randomized factorial study on concurrent and adjuvant chemotherapy for advanced nasopharyngeal carcinoma

Abstract

Purpose/Objective(s): To update the results of a randomized factorial trial studying the role of concurrent chemoradiation (CRT) and adjuvant chemotherapy (AC) for advanced nasopharygngeal carcinoma (NPC). Materials/Methods: Ho’s stage T3 or N2 /N3 or 4cm neck node, M0 disease were eligible. Patients were first randomized to receive CRT or radiotherapy (RT) alone and then further randomized to receive AC or no AC after CRT/RT. CRT involved UFT (uracil and tegafur in 4:1 molar ratio) 200mg, 3 times a day, during RT. 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, after CRT/RT. There were 4 treatment arms: 1. RT, 2. CRT, 3. RT AC, 4. CRT AC. To analyze the efficacy of CRT, arms 1 and 3 were compared with arms 2 and 4 (i.e. RT vs. CRT). To analyze the efficacy of AC, arms 1 and 2 were compared with arms 3 and 4 (i.e. no AC vs. AC). Analysis was performed according to intention to treat. Persistent disease or recurrence in nasopharynx (NP) or neck nodes and distant metastases were considered disease failure. Death after recurrence was considered due to NPC. Results: From May 1995 to October 2001, 222 patients were recruited. 3 patients were excluded from analysis because of major protocol violation. Median follow up time of 219 patients in analysis was 65 months. The median age was 45. Median dose to NP and neck were 68Gy and 66Gy, respectively. There were 55, 53, 54, 57 patients in arm 1, 2, 3, 4 respectively. The 5-year loco-regional control rate and distant metastases-free survival of arm 1, 2, 3, 4 were 64.2%, 74.8%, 78.7%, 81.1% and 74.2%, 85.8%, 67%, 82.4% respectively. The 5-year failure-free and disease-specific survivals of the 4 arms were and 54%, 69%, 54.6%, 66.4% and 77.1%, 79.8%, 67.7%, 81.4% respectively. CRT significantly improved the distant metastases-free and failure-free survival (p0.02 and 0.038 respectively). The difference in disease specific survivals was not statistically significant (p0.075). The use of AC failed to improve survival on all measures. Multivariate analysis showed only CRT as significant prognostic factor for failure-free survival. Age, T stage, N stage and CRT were significant prognostic factors for disease-specific survival. The use of AC was not significant for failure-free or disease-specific survival. Conclusions: CRT significantly reduced distant metastases and improved failure-free survival for patients with advanced NPC. There is an improvement of disease-specific survival after adjusting for age and stage of disease. AC failed to improve survival. The positive effect of CRT was confirmed on long term follow-up.