Re-treatment of nasopharyngeal carcinoma by sequential chemo-radiotherapy with or without cetuximab

Abstract

PURPOSE/OBJECTIVE(S): Patients with loco-regionally recurrent nasopharyngeal carcinoma (NPC) frequently require external beam radiotherapy for re-treatment but treatment results are unsatisfactory with poor control rate and high risk of late complications. Over-expression of epidermal growth factor receptor (EGFR) is common in NPC and combination of anti-EGFR targeted therapy with ERT may improve outcome. MATERIALS/METHODS: Sixteen consecutive patients with loco-regional recurrence of NPC not amenable to surgery or brachytherapy were enrolled into a phase II study using induction chemotherapy consisted of gemcitabine and carboplatin for 3 cycles followed by re-irradiation using intensity-modulated radiotherapy. Cetuximab was administered at a loading dose of 400mg/m2 1 week before radiotherapy followed by weekly dose of 250mg/m2 during treatment (Group 1). Treatment outcome of this study group was compared with a historical cohort of 17 patients treated also by sequential chemo-radiotherapy using similar regimens and techniques but without cetuximab (Group 2). Loco-regional progression-free (LRPF) rate and overall survival rate (OS) were estimated using Kaplan-Meier method and differences compared with log–rank test. RESULTS: More patients in Group 1 had advanced nodal disease at recurrence (rN1-2: 37.5% in Group 1 vs. 6% in Group 2) whereas more patients in Group 2 had advanced primary tumor at recurrence (rT3–4:62% in Group 1 vs. 100% in Group 2). All patients completed chemo-radiotherapy and the median dose was 54 Gy in both groups. The median no. of cycles of cetuximab in Group 1 was 6 (range, 2 – 7). Acute toxicities during radiotherapy were mild and the incidence of Grade 3 mucositis was 12.5% in Group 2 and 6% in Group 2. One patient in group 1 developed Grade 3 acneiform rash. Median follow-up time for surviving patients was 22 months in Group 1 and 61 months in Group 2. One-year and 2-year LRPF rates were 43% and 36% in Group 1 compared with 44% and 36% in Group 2 (p = 0.91). One-year and 2-year OS rates were 93% and 79% in Group 1 compared with 94% and 82% in Group 2 (p = 0.37). CONCLUSIONS: Re-treatment of loco-regionally recurrent NPC by sequential chemo-radiotherapy with concurrent cetuximab was generally well-tolerated. The short term tumor control and survival rates appeared to be comparable but not superior to historical control using similar treatment but without cetuximab.