| Objective:This prospective study aimed to evaluate the efficacy and toxicities of continuous infusion of recombinant endostatin(Endostar)fortnightly combined with etoposide,cisplatin(EP)and concurrent radiotherapy in the treatment of inoperable locally advanced NSCLC.Methods:This was a single-arm,phase Ⅱ clinical study,in which patients with untreated pathologically confirmed NSCLC and inoperable locally advanced lung cancer were included.All patients were given standard concurrent chemoradiotherapy.Endostar of 7.5 mg/m2/24 hours was administrated with continuous intravenous pumping for 120 hours fortnightly,at beginning of 5 days prior to the starting of radiotherapy.Radiation doses were 60-66 Gy/30-33 fractions for 6-7 weeks.Two cycles of EP regimen(etoposide 50 mg/m2,dl-5,cisplatin 50 mg/m2,on days 1,8,28 days/cycle)were delivered.The primary endpoint was progression-free survival(PFS).The secondary endpoints were objective response rate(ORR)and overall survival(OS),locoregional progression-free survival(LPFS),distant metastasis-free survival(DMFS),and adverse events(AEs).The Kaplan-meier method was used to analyze the survival,and univariate analysis was performed using the log-rank test.Results:From November 2012 to June 2015,a total of 73 patients were enrolled,and 67 patients were evaluable.The median age was 59 years.Sixty-six percent of the patients had squamous cell carcinoma.Grade≥3 AEs occurred in 58.2%of the patients.The most common Grade≥3 AE was leukopenia(44.8%).The ORR was 76.1%.The median PFS and OS were 13.3 months and 34.7 months,respectively.The 2-year PFS,OS,LPFS and DMFS were 34.8%,59.9%,54.7%and 68.5%,respectively.Conclusions:For inoperable locally advanced NSCLC patients,continuous intravenous Endostar fortnightly combined with concurrent EP and radiotherapy got preferable OS,promising 2-year PFS with tolerable toxicities,although it did not prolong median PFS at preliminary analysis.It is worthy of further phase Ⅲ controlled clinical study.Objective:The phase Ⅱ prospective studies showed that the treatment of inoperable locally advanced NSCLC with Endostar administrated fortnightly combined with concurrent chemoradiotherapy tented to prolong survival,but there was a lack of controlled studies.This study was to evaluate 5 years survival of Endostar combined with concurrent radiotherapy in the treatment of inoperable locally advanced NSCLC.Methods:Patients from some prospective studies with long-term follow-up data were included as two cohorts.All the patients were inoperable locally advanced NSCLC and initially treated.One group was treated with concurrent chemoradiotherapy combined with Endostar(CCRT+Endostar group).Endostar was administrated 1 week before chemoradiotherapy and every other week during chemoradiotherapy.The other group received concurrent chemoradiotherapy(CCRT group).The radiotherapy was performed using three-dimensional conformal(3D-CRT)or intensity modulated radiotherapy(IMRT)techniques.Both groups of patients received platinum-based regimen concurrent chemotherapy.The outcome of survival was decided from the beginning of initially treatment to the 5th year of follow-up.Those who still survived but follow-up time was less than 5 years were excluded from the 5 years survival analysis.Results:105 patients were included in the CCRT+Endostar group,and 91 patients in the CCRT group.87(82.9%)and 76(83.5%)patients were male,and 18(17.1%)and 15(16.5%)patients were female in the two groups,respectively.64(61%)and 45(49.5%)were squamous cell carcinoma,respectively.34.3%and 36.3%were stage IIIA,65.7%and 63.7%were stage ⅢB,respectively.89.5%and 79.1%patients received radiotherapy dose of≥60 Gy,respectively(p=0.044).The median follow-up time was 73.7 months(95%CI:69.6-77.7 months)and 81.3 months(95%CI:72.1-90.4 months),respectively.The median survival time was 26.9 months(95%CI:22.5-31.3 months)in CCRT+Endostar group and 17.4 months(95%CI:15.0-19.9 months)in CCRT group.The 5-year survival rate was 27.9%and 15.4%,respectively,(HR=0.654,95%CI:0.48-0.891,p=0.007).In the subgroup of radiotherapy dose of≥60 Gy,the median survival time was 28.4 months(95%CI:22.2-34.7 months)in CCRT+Endostar group and 18.3 months(95%CI:13.6-23.0 months)in CCRT group.The 5-year survival rate was 30.1%and 18.4%,respectively,(HR=0.658,95%CI:0.466-0.928,p=0.017).Conclusion:Patients with inoperable locally advanced NSCLC who were treated with Endostar delivering fortnightly combined with platinum-based concurrent chemoradiotherapy obtained significantly longer 5 years survival time than them with CCRT.Objective:There are two main choices of administration route of recombinant human endostatin(Endostar)available and the treatment options of concurrent chemoradiotherapy(CCRT)have changed over time.The aim of this study was to observe the long-term efficacy and safety of different administration routes of Endostar combined with CCRT.Methods:Patients with unresectable locally advanced non-small cell lung cancer(NSCLC)from two phase Ⅱ trials were included as two cohorts.Both were treated with Endostar combined with CCRT.Endostar was administrated by intravenous injection(7.5 mg/m2/day,for seven days)in the Ⅳ arm and by continuous intravenous pumping(7.5 mg/m2/24 hours,for 120 hours)in the CIV arm.Results:A total of 48 patients were included in the Ⅳ arm and 67 patients in the CIV arm.The median progression-free survival(PFS),overall survival(OS),local progression-free survival(LPFS)and distant metastasis-free survival(DMFS)in the Ⅳarm and CIV arm were 9.9 months versus 15.4 months(HR=0.751,95%CI 0.487-1.160,p=0.200),24.0 months versus 38.5 months(HR=0.746,95%CI 0.473-1.178,p=0.209),32.3 months versus 27.1 months(HR=1.193,95%CI 0.673-2.115,p=0.546),20.1 months versus 49.7 months(HR=0.603,95%CI 0.351-1.036,p=0.067).The one,three,five-year PFS in the Ⅳ arm and CIV arm was 45.8%,18.3%,18.3%versus 52.9%,31.4%,27.7%,respectively,and the one,three,five-year OS was 81.2%,31.1%,31.1%versus 82.1%,50.3%,41%,respectively.Incidence of non-hematological adverse reactions were numerically lower in the CIV arm than the Ⅳ arm.But the incidence of hematological toxicity was opposite.Conclusions:At present,it has not been determined that Endostar was administrated by CIV with concurrent chemoradiotherapy is superior to by Ⅳ in terms of survival and safety in the treatment of inoperable locally advanced NSCLC.Further head-to-head studies are needed. |
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