Concurrent Chemoradiotherapy Plus Cytokine-Induced Killer Cells Therapy In Patients With Locoregionally Advanced Nasopharyngeal Carcinoma: A Ten-Year-Follow-Up Of A Randomized, Phase Ⅱ Study

Background: Nasopharyngeal carcinoma(NPC)is a head and neck cancer that occurs frequently in South Asia and southern China.The standard of care is concurrent chemoradiotherapy(CCRT).After CCRT treatment,the survival rate of nasopharyngeal carcinoma has been improved,however,approximately 25% of patients with locoregionally advanced nasopharyngeal carcinoma still fail after receiving CCRT,the main cause of death was distant metastasis.We aimed to evaluate the efficacy and safety of Cytokine-Induced Killer cells(CIK)therapy in combination with concurrent chemoradiotherapy for the treatment of patients with locoregionally advanced nasopharyngeal carcinoma.Methods: This is a single-center,randomized,phase II study,Patients from Sun yat-sen university cancer center with locoregionally advanced nasopharyngeal carcinoma were randomized in a 1:1 ratio to CIK therapy group(receive concurrent chemoradiotherapy plus CIK consolidation therapy)or control group(concurrent chemoradiotherapy alone).The primary endpoint was overall survival(OS)and disease-free survival(DFS).Secondary end points included safety.The baseline characteristics of patients were compared by Chi-square test or Fisher’s exact test.Survival curves were drawn by the Kaplan-Meier analyses.Cox proportional hazard regression models were used to analyze clinical variables of two groups.Results: From March 5 2008 to June 19 2010,a total of 65 patients with locoregionally advanced nasopharyngeal carcinoma in Sun Yat-sen University Cancer Center were screened,then 58 patients were included in this trial(29 in the CIK therapy group and 29 in the observation group).The median follow-up time was 144.70 months.The 10-year disease-free survival rate in the CIK therapy group was significantly higher than that in the control group(82.5% versus 61.3%;hazard ratio for recurrence or death,0.258;95% confidence interval [CI],0.094-0.712;P=0.005).The 10-year overall survival rate was 86.2% and 67.5%,respectively;(hazard ratio for death,0.377;95% confidence interval [CI],0.131-1.087;P=0.06).multivariate analysis indicated that CIK therapy,EBV-DNA levels,tumor TNM stage were prognostic factor for DFS,the CIK therapy was not the prognostic factor for OS.The main adverse effects of CIK was fever which can return to normal after symptomatic treatment.The incidence of acute adverse events of grade 3 or 4 during CCRT was 23.1% in the CIK therapy group and 17.2% in the control group.The most common adverse events of grade 3 is mucositis,followed by decreased appetite,marrow suppression.Conclusions: In patients with locoregionally advanced nasopharyngeal cancer,CIK treatment was shown to improve their DFS with no serious adverse events.(Chinese Clinical Trial.gov number: Chi CTR-TRC-08000262.)...