Release Of The Integrated Treatment Of Locally Advanced Nasopharyngeal Carcinoma Multi-center, Open, Randomized, Controlled Study

PART1CLINICAL EFFICACY OF INDUCTIONCHEMOTHERAPY WITH DOCETAXEL PLUSNEDAPLATIN FOLLOWED BY CONCURRENTNEDAPLATIN WITH RADIOTHERAPY FOR LOCALLYADVANCED NASOPHARYNGEAL CARCINOMAObjective To evaluate the efficacy,toxicity and treatment compliance of patientswith locoregionally advanced nasopharyngeal carcinoma (NPC) treated withinduction chemotherapy with docetaxel plus nedaplatin followed by concurrentnedaplatin with radiotherapy.Methods From November2011to November2012,405patients accrued from5centers with nondisseminated NPC who received initial radiotherapy wereanalyzed. The stage distribution (by AJCC,2009) was187and218patients inStage III and IVa+IVb. According to the principle of stratified random,thepatients who received IMRT served as the IMRT group,and others who acceptedCRT formed the CRT group. In each group, they were randomly assigned totreatment group and control group. The patients in treatment group received2cycles of induction chemotherapy with docetaxel(DOC,65mg/m2/d1) plusnedaplatin(NDP,80mg/m2/d1) every3week, followed by6cycles of concurrentchemotherapy with NDP(40mg/m2/d1) every week, and received2cycles ofinduction chemotherapy with DOC(65mg/m2/d1) plus cisplatin (CDDP,80mg/m2/d1) every3week, followed by6cycles of concurrent chemotherapywith CDDP(40mg/m2/d1) every week in control group. The prescription doses of IMRT were as follows:68~74Gy/30~33fraction to PTVnx,68~70Gy/30~33fraction to PTVnd,60~64Gy/30~33fraction to PTV1,50~56Gy/30~33fractionto PTV2. CRT consisted of68~74Gy/34~40fraction to PTVnx,68~72Gy/34~36fraction to PTVnd,60~64Gy/30~32fraction toPTV1,50~54Gy/25~27fraction to PTV2.Results (1)IMRT group: There were223patients in the group. More patients inthe treatment group had completed two cycles of induction chemotherapy andsix cycles of concurrent chemotherapy than those in control group(89cases vs.69cases, x2=2.487,P=0.013).The primary gross volume (GTVnx) of thetreatment group and the control groug reduced17.12cm3and16.22cm3afterinduction chemotherapy,respectively（t=1.045,P＝0.297）. The volume of theinvolved lymph nodes(GTVnd) of the treatment group and the control grougreduced8.75cm3and7.70cm3,respectively(t=1.556,P＝0.121).There was nosignificant difference in complete response rate between the two groups threemonths after treatment(P>0.05). During induction chemotherapy,the mostcommon acute toxicities were leukocytopenia,neutropenia and nausea/vomiting.No significant differences in leukocytopenia,neutropenia could be detectedbetween the two groups(P>0.05). In the treatment group,31.0%of the patientshad Grade1nausea/vomiting,32.7%had Grade2,5.3%had Grade3.In thecontrol group,31.8%had Grade1,43.6%had Grade2,11.8%had Grade3.Therewas significant difference between the two groups(Z=3.377,P=0.001).Morepatients in the control group suffered from anemia than in the treatmentgroup(Z=2.820,P=0.005). The most common hematologic toxicities wereleukocytopenia,neutropenia and thrombocytopenia during concurrentchemoradiotherapy,which occured in the treatment group more than the controlgroup(p<0.05).Anemia is a frequent toxicity as well,and more occured in the control group(P<0.05).The most common non-hematologic toxicities werenausea/vomiting,mucositis, dermatitis, and xerostomia.Less patients in thetreatment group suffered from nausea/vomiting than in the controlgroup(Z=2.270,P=0.023).There’s no infection febrile neutropenia andhemorrhage during treatment.The most common late toxicity wasxerostomia,and the severity decreased over time.For all the patients,the2-yearlocal recurrence-free survival(LRFS),regional recurrence-free survival(RRFS),distant metastasis-free survival (DMFS),progression-free survival(PFS)and overall survival(OS) were97.9%,98.0%,96.6%,92.6%and100%,respectively. There were no significant differences between thetreatment group and the control group in the2-year LRFS(97.8%vs.98.0%;P=0.957)、 RRFS(100%vs.95.9%;P=0.143)、 DMFS(98.6%vs.94.5%;P=0.531)、 PFS(95.1%vs.88.5%;P=0.420) and OS(100%vs.100%;P>0.05). In univariate analysis, N stage was significant predictor ofPFS(x2=4.010,P=0.045). However,multivariate analysis showed no independentpredictive factors.(2)CRT group: There were182patients in the group. More patients in thetreatment group had completed two cycles of induction chemotherapy and sixcycles of concurrent chemotherapy than those in control group(72cases vs.63cases, x2=2.014,P=0.044).GTVnx of the treatment group and the control grougreduced15.98cm3and15.63cm3after induction chemotherapy,respectively（t=0.444,P＝0.658）. GTVnd of the treatment group and the control grougreduced7.81cm3and6.95cm3,respectively (t=1.244,P=1.777).There was nosignificant difference in complete response rate between the two groups threemonths after treatment(P>0.05). During induction chemotherapy,the mostcommon acute toxicities were leukocytopenia,neutropenia and nausea/vomiting.No significant differences in leukocytopenia,neutropenia couldbe found between the two group(P>0.05). In the treatment group,34.8%of thepatients had Grade1nausea/vomiting,33.7%had Grade2,2.2%had Grade3.Inthe control group,24.7%had Grade1,49.5%had Grade2,3.2%had Grade3.There was significant difference between the twogroups(Z=1.991,P=0.042).More patients in the control group suffered fromanemia than in the treatment group(Z=4.714,P=0.000). The most commonhematologic toxicities were leukocytopenia,neutropenia thrombocytopeniaduring concurrent chemoradiotherapy,which occured in the treatment groupmore than in the control group(p<0.05).Anemia is a frequent toxicity as well,andmore occured in the control group(P<0.05).The most common non-hematologictoxicities were nausea/vomiting,mucositis, dermatitis, and xerostomia.Lesspatients in the treatment group suffered from nausea/vomiting than in the controlgroup(Z=2.039,P=0.041). There’s no infection febrile neutropenia andhemorrhage during treatment. The most common late toxicity wasxerostomia,and the severity of it decreased over time.For total of thepatients,the2-year LRFS, RRFS, DMFS,PFS and OS were94.0%,95.5%,94.8%,84.6%and100%,respectively. There were no significantdifferences between the treatment group and the control group in the2-yearLRFS(95.2%vs.92.9%;P=0.674)、 RRFS(93.0%vs.98.5%;P=0.590)、DMFS(93.2%vs.94.2%;P=0.981)、 PFS(81.5%vs.85.8%;P=0.997) andOS(100%vs.100%;P>0.05). In univariate analysis, N stage and clinical stagewere significant predictors of PFS(x2=4.874, P=0.027and x2=5.187, P=0.023,respectively). However,multivariate analysis showed no independent predictivefactors.Conclusions Treatment with docetaxel plus nedaplatin is effective and well-tolerated in patients with locoregionally advanced NPC． PART2TREATMENT RESULTS OF INTENSITY-MODULATEDRADIOTHERAPY AND CONVENTIONAL RADIOTHERAPYFORLOCOREGIONALLY ADVANCED NASOPHARYNGEALCARCINOMAObjective To analyze the treatment results of patients with locoregionallyadvanced nasopharyngeal carcinoma (NPC) treated by different external beamradiation therapy techniques.Methods All the405patients accrued from5centers were eligible foranalysis.According to the grouping method of part1,the patients were dividedinto IMRT group and CRT group, in which the radiation technique andchemotherapy regimens were as same as those in part1.Results There was no significant difference in complete response rate betweenthe IMRT group and the CRT group three months after treatment(P>0.05). Themost common acute hematologic toxicities wereleukocytopenia,neutropenia,anemia and thrombocytopenia, in which nosignificant differences could be found between the two groups(P>0.05). Themost common acute non-hematologic toxicities were nausea/vomiting,mucositis,dermatitis, and xerostomia.There was no significant differences innausea/vomiting and mucositis between the two groups(P>0.05).In the IMRTgroup,71.0%of patients had Grade1dermatitis,22.2%had Grade2,4.1%hadGrade3.In the CRT group,47.8%had Grade1,39.6%had Grade2,11.0%hadGrade3.None had Grade4dermatitis.There was significant difference betweenthe two groups(Z=5.038,P=0.000).Xerostomia was the most common adverseevent after radiotherapy.At the end of treatment,20.4%of patients underwent IMRT had Grade1,75.1%had Grade2, and1.8%had Grade3xerostomia.Whereas13.7%of patients underwent CRT had Grade1,74.2%hadGrade2, and12.1%had Grade3xerostomia.There was no significant differencein xerostomia between the two groups(Z＝3.967,P＝0.000). At12months aftertreatment, only12.2%of the IMRT group had Grade2and none had Grade3or4xerostomia,whereas59.9%of the CRT patients had Grade2xerostomia,10.4%still had Grade3xerostomia. Less patients in the IMRT group sufferedfrom xerostomia than in the CRT group(Z=11.11,P=0.000).For total of thepatients,the2-year LRFS, RRFS, DMFS, PFS and OS were96.1%,96.9%,95.8%,88.9%and100%, respectively. No significant differences were detected betweenthe two groups in the2-year LRFS(97.9%vs.94.0%; x2=1.957, P=0.162),RRFS(98.0%vs.95.5%; x2=0.479, P=0.489),DMFS(96.6%vs.94.8%;x2=0.405,P=0.525), PFS(92.6%vs.84.6%; x2=2.580,P=0.108) and OS(100%vs.100%;P>0.05).In univariate analysis,clinical stage was significant predictor ofRRFS(x2=4.660，P=0.031)and DMFS(x2=6.682，P=0.010）.N stage and clinicalstage were significant predictors of PFS(x2=9.494,P=0.002andx2=8.644,P=0.003).Multivariate analysis showed that clinical stage wasindependent predictive factor for PFS(x2=5.718,P=0.017).Conclusions (1)Compared with CRT, IMRT has the tendence to improveshort-term effect of the patients.(2)IMRT has the tendence to improve tumorcontrol probability.(3)More patients in CRT group suffer from acute and latetoxicities than those in IMRT group.