Control of Regional Metastasis after Induction Chemotherapy and Radiotherapy for Nasopharyngeal Carcinoma

Purpose: To study the impact of adding induction chemotherapy to radiotherapy on the long term control of regional metastasis and survival in patients with nasopharyngeal carcinoma (NPC). Patients and Methods: Between February 1988 and August 1993, 240 NPC patients with Ho’s T3 stage, N2-3 stage, or nodal size ≥3 cm were recruited onto two randomized trials comparing induction chemotherapy followed by radiotherapy (CT+RT) and radiotherapy alone (RT) using a similar treatment protocol. Of these, 210 patients (105 in each treatment arm) had cervical nodal metastasis and were included in the analysis. Patients in the CT+RT arm received 2-3 cycles of cisplatin 60mg/m2 day 1 + epirubicin 110mg/m2 day 1 followed by radiotherapy. Radiotherapy technique and dose were similar in both arms. All 210 patients completed the treatment and were evaluable. The median follow-up time was 71 months (5-152 months). Results: The overall response rate of nodal disease to chemotherapy was 86% and the complete response (CR) rate was 44%. At the end of radiotherapy, 92% of patients in the CT+RT arm and 86% in the RT arm achieved CR in the neck (p=0.12). At the time of analysis, failures in the neck occurred in 16% of patients in the CT+RT arm and 25% in the RT arm (p=0.12). The 5-year nodal relapse-free survival rates in the CT+RT and RT arm were 83% and 75%, respectively (p=0.13). Most neck failures (81%) occurred during the first 36 months of follow-up. Radical neck dissection successfully salvaged 41% of neck failures in the CT+RT arm and 46% in the RT arm. The 5-year distant metastases-free survival rates were 70% in the CT+RT arm and 68% in the RT arm (p=0.56), and the corresponding 5-year disease-specific survival rates were 66% and 68%, respectively (p=0.55). In subgroup analysis, no significant differences in regional control and survival could be found in patients with advanced N stage disease as defined by either Ho’s N2-3 stage or AJCC N2-3 stage. In patients with nodal size >6 cm, the 5-year nodal relapse-free survival rates in the CT+RT and RT arm were 84% and 64%, respectively, but the difference was not significant (p=0.1). Complete responders to chemotherapy had significantly improved regional control and survival when compared with non-complete responders. Conclusion: Induction chemotherapy does not appear to improve the regional control and survival in NPC patients with regional metastasis when compared to radiotherapy alone, and is not recommended as a routine treatment outside the context of clinical trial.