Long-term results of the phase II dose and volume de-escalation trial for locoregionally advanced nasopharyngeal carcinoma.

OBJECTIVE: Patients with locoregionally advanced nasopharyngeal carcinoma (LANPC) were assigned to dose and volume de-escalated intensity-modulated radiation therapy (IMRT) based on response to induction chemotherapy (IC) to limit treatment related toxicity while preserving efficacy. METHODS AND MATERIALS: A single-arm de-escalated phase II trial was performed in this study. Patients with LANPC received two cycles of IC with docetaxel 60 mg/m(2) d1, cisplatin 25 mg/m(2)/day d1-3 and 5-fluorouracil 500 mg/m(2)/day d1-5 q21d, followed by IMRT. The gross tumor volume of the primary intracavity nasopharyngeal tumor and involved lymph nodes were delineated based on the post-IC tumor extension. Part of the prescribed doses were reduced from 70.4 Gy to 66 Gy for T3-4 diseases. The primary end point was 5-year progression-free survival (PFS) in stage III and IVA-B NPC compared with historical controls of 50% and 35%. RESULTS: Between January 2010 and November 2013, 48 and 83 eligible patients with stage III and IVA-B NPC were accrued to this trial. With a median follow-up of 92 months, the 5-year and 8-year estimated PFS were 89.6% and 76.0%, 63.9% and 58.0% for patients with stage III and IVA-B disease, which were all improved in comparison with historical controls. Grade 3 acute mucositis were developed in 27.5% patients. Cranial neuropathy and asymptomatic temporal lobe necrosis were found in 2.3% and 1.5% patients. CONCLUSION: Dose and volume de-escalated IMRT was associated with high PFS and mild late neurological toxicities for IC responders. Further exploration of de-escalation strategies in appropriate patients is needed. CLINICAL TRIAL REGISTRATION: Clinical trials.gov identifier: NCT03389295.