Treatment Outcomes of 257 Patients with Locoregionally Advanced Nasopharyngeal Carcinoma Treated with Nimotuzumab Plus Intensity-Modulated Radiotherapy with or without Chemotherapy: A Single-Institution Experience

Abstract

Objectives: To report the long-term outcome and toxicity of locoregionally advanced nasopharyngeal carcinoma (LA NPC) treated with nimotuzumab (h-R3) plus intensity-modulated radiotherapy (IMRT) with or without chemotherapy.

Methods: From May 2008 to March 2014, 3022 newly histology-proven, nonmetastatic NPC patients were retrospectively reviewed; among them, 257 patients treated with h-R3 were enrolled in this study. The patients' age range was between 10 and 76 years. The distribution of patients by disease stage was 150 (58.4%) in stage III, 88 (34.2%) in stage IV A, and 19 (7.4%) in stage IV B. All the patients received the treatment of h-R3 plus IMRT, and from them, 239 cases were also treated with cisplatin-based chemotherapy. Acute and late radiation-related toxicities were graded according to the Acute and Late Radiation Morbidity Scoring Criteria of Radiation Therapy Oncology Group. The accumulated survival was calculated according to the Kaplan-Meier method. Log-rank test was used to compare the survival difference. Multivariate analysis was performed using Cox's proportional-hazard model.

Results: All 257 patients had completed combined treatment; 231 patients received h-R3 plus IMRT with induction chemotherapy (IC), while 26 patients received only h-R3 plus IMRT. With a median follow-up of 48 months (range, 13-75 months), the estimated 5-year local recurrence-free survival, regional recurrence-free survival, distant metastases-free survival, progression-free survival, and overall survival (OS) rates were 94.3%, 94.8%, 91.9%, 83.4%, and 86.2%, respectively. Univariate analysis showed that age, T stage, clinical stage, and IC were related with OS. Multivariate analysis indicated that T stage and IC were independent prognostic factors for OS. The incidence of grade 3 to 4 acute mucositis and leukocytopenia was 10.9% and 19.8%, respectively, with no cases of skin rash and infusion reaction. Xerostomia was the most common late complication, and the degree of dry mouth in most survivors was mild to moderate at the last follow-up time.

Conclusion: h-R3 plus IMRT with or without chemotherapy showed promising outcomes in terms of locoregional control and survival without increasing the incidence of radiation-related toxicities for patients.

Figure 1

Flowchart of patients.

Figure 2

Kaplan-Meier estimates of the survival in patients with nasopharyngeal carcinoma. (A) LRFS; (B) RRFS; (C) DMFS; (D) PFS; (E) OS.

Figure 3

Kaplan-Meier estimates of the OS in nasopharyngeal carcinoma patients for different variable. (A) Overall survival for T stages; (B) overall survival for with IC versus without IC; (C) overall survival for <60 years versus ≥60 years; and (D) overall survival for clinical stage.

Figure 4

Kaplan-Meier estimates of the PFS in nasopharyngeal carcinoma patients for univariate. (A) PFS for clinical stages; (B) PFS for N stages; (C) PFS of patients with or without AC; and (D) PFS for tumor response.

Figure 5

Kaplan-Meier estimates of PFS in nasopharyngeal carcinoma patients by subgroup analysis. (A) PFS for total dose of h-R3 in female patients; (B) PFS for total dose of h-R3 in patients with non-CR.