Comparison Of Three-Day And One-Day Dosing Of Cisplatin In A Three-Week Regimen In Concurrent Chemoradiotherapy For Nasopharyngeal Carcinoma

Background: Nasopharyngeal carcinoma(NPC)is an epithelial carcinoma,originating in the mucous membrane of the nasopharynx.In the nasopharynx,tumors are often observed in the recesses of the pharynx.The geographic distribution of NPC is unique in that the incidence of NPC is relatively rare globally,but 70% of cases occur in East and Southeast Asia.Cisplatin-based concurrent chemoradiotherapy(CCRT)is the treatment of choice for non-distant metastatic nasopharyngeal carcinoma in both domestic and international guidelines,but there is no uniform standard for how cisplatin should be administered.We compared the efficacy and toxicity of one-day or three-day dosing of cisplatin in a three-week regimen during CCRT for NPC.Method: The retrospective analysis collects 228 newly NPC patients,diagnosed and treated by CCRT alone at the Sun Yat-sen University Cancer Center from 2009 to 2015,all of whom received cisplatin-based concurrent chemoradiotherapy.In the three-day group,25-35 mg/m2 of cisplatin was delivered without hydration on three days every three weeks.In the one-day group,75-100/m2 of cisplatin was delivered with hydration on one day every three weeks.The majority of patients in both groups received 2 cycles of concurrent chemotherapy and others received 3 cycles.In this study,survival curves were plotted using the Kaplan-Meier method,and the log-rank method was used to compare whether there was a statistical difference in overall survival(OS),disease-free survival(DFS),distant metastasis-free survival(DMFS)and local recurrence-free survival(LRFS)between the two groups of patients.Independent prognostic factors of survival were identified with univariate and multivariate Cox proportional hazards regression analyses.For treatment-related toxicity in the two groups,we compared the incidence of toxicity between the two groups by Chi-square test or by checking Fisher’s exact test for statistical differences.The incidence of treatment toxicity was compared between the two groups by Chi-square test or by checking Fisher’s exact test for statistical differences.Result: A total of 228 patients with stage I to IVA nasopharyngeal carcinoma diagnosed between 2009 and 2015 were included,of which 62(27.2%)patients received three-day dosing and 162(72.8%)patients received one-day dosing during CCRT.The statistical difference of chemotherapy cycles(58(93.5%)with 2 cycles in the three-day group vs.118(71.1%)in the one-day group;p < 0.001)and cumulative cisplatin dose(163mg/m2(median)in the three-day group vs.195mg/m2(median)in the one-day;p < 0.001)were found between two group.Demographics and baseline disease characteristics were balanced between two groups.There is no statistical difference in 5-years OS,DFS,LMFS and LRFS rates between the two groups(three-day group vs.one-day group: OS = 89.9% vs.88.9%,p = 0.421;DFS = 70.4% vs.77.0%,p = 0.661;DMFS = 92.9% vs.95.7%,p = 0.377;LRFS = 85.7% vs.94.2%,p = 0.141).In the subgroup analysis selected patients with stage III-IVA,there was no statistical difference in 5-year OS(three-day vs.one-day: 89.6% vs.86.6%,p = 0.175)and 5-year DFS(three-day vs.one-day: 67.2% vs.72.9%,p = 0.831)between two groups.The univariate logistic regression analysis showed that the EBV DNA(>4000 copy/ml)and smoking are the significant risk factors for OS(P= 0.04 and 0.010,respectively)and EBV DNA(>4000 copy/ml),smoking,N stage(N2-3)and clinical stage(III-IVA)are the significant risk factors for DFS(P= 0.021,0.009,0.002 and 0.005,respectively).The multivariate logistic regression analysis showed that smoking is the independent risk factor for OS(HR = 2.863,95% CI = 1.269-6.460,P = 0.011),and EBV DNA(>4000 copy/ml)and clinical stage(III-IVA)is the independent risk factor for DFS(EBV DNA: HR = 1.835,95% CI = 1.086-3.101,P = 0.023;clinical stage: HR = 5.961,95% CI = 1.461-24.319,P = 0.013).The cisplatin dosing regimens were not OS and DFS prognostic factors.In treatment toxicity,the overall three-day group was lower than the one-day group.In incidence of leukopenia,anemia,impaired renal function,hypomagnesemia,nausea,and vomiting,the three-day group was significantly lower than the one-day group.Conclusions: In a three-week cisplatin regimen of CCRT for NPC,three-day dosing of cisplatin can achieve the same efficacy as one-day dosing with reduced treatment-related toxicity.The three-day dosing approach eliminates the need for hydration and is more convenient and safer for clinical use,with patients receiving chemotherapy on an outpatient basis.This study can help physicians choose the appropriate method of cisplatin administration in clinical practice and provide a reference for related prospective studies.