A Clinical Study Of Recombinant Human Endostatin In Different Administration Sequences Combination With Paclitaxel And Cisplatin In The Treatment Of Non-small Cell Lung Cancer

Objective:To investigate the toxicity and efficacy ofrecombinant human endostatin in different administration sequencescombination with paclitaxel and cisplatin treatment of non-small cell lungcancer,and to determine the concentration of cisplatiin and paclitaxel inhuman plasma after treatment,and to compare the anti-angiogenic effect,toarrive at the optimal administration sequences the endostarcombination with chemotherapy drugs. Methods:30cases of histologically orcytologically diagnosed in the initial treatment or retreatment NSCLS neededchemotherapy were enrolled into the study and divided to three groups: thegroup used paclitaxel after Endostar and cisplatiin used4days(hereinafterreferred to as " the before-after group ")、the group used paclitaxel、cisplatiin and Endostar at the same day(hereinafter referred to as "Endo+TPgroup")、the group used paclitaxel and cisplatiin only(hereinafter referred toas the "control group "),to receive2cycles of chemotherapy. To observe thetoxicity and evaluate the efficacy after2cycles of chemotherapy.To drawvenous blood when3h after administration of paclitaxel and72h afteradministration of cisplatin to measure the blood concentration.Used CTperfusion imaging before treatment and after the two cycle chemotherapy.Results: endostar treatment group (including the before-after group and the Endo+TP group) and the control group after treatment emerge varying degreesof drug toxicity,mainly:(1)gastrointestinal reactions (mainlynausea,vomiting);(2)myelosuppression (mainly leukopenia andthrombocytopenia);(3)liver dysfunction;(4)muscle pain;(5)and alopecia. Allpatients were not emerging impaired renal function arrhythmia or severecoronary artery disease, and no adverse events or serious adverse events. Theincidence endostar treatment group and the control group of patients with drugtoxicity was no significant difference (P>0.05). The before-after group CR1(12.5%), PR2(25%), SD4(50%), PD1patients (12.5%), the effective ratewas37.5%; Endo+TP group CR0patients (0.0%),PR2(28.6%), SD5(71.5%),PD0patients (0.0%),the effective rate was28.6%; the control group CR2(13.3%), PR2(13.3%), SD10patients (66.7%), PD1(6.7%), the effectiverate was26.7%. The before-after group has the same time efficient comparedwith the Endo+TP group, P>0.05, the difference was not statisticallysignificant. The before-after group compared with chemotherapy alone group,the difference was not statistically significant (P>0.05), while Endo+TP groupcompared with the chemotherapy alone group,P>0.05, the difference is stillnot statistically significant. The blood concentration of paclitaxel in thebefore-after group is6.144ug/ml,while the concentration of paclitaxel inpatients blood mean of5.227ug/ml,blood concentrations of paclitaxel inpatients in the control group were number5.501ug/ml. After statisticalanalysis, P>0.05,indicating that the overall difference between the three groups was not statistically significant. Patients in the before-after group havemean of blood concentrations of cisplatin with4.35ug/ml,while groupconcentrations of cisplatin in patients with venous mean of4.19ug/ml, theconcentration in the blood of patients in the control group mean of cisplatin4.30ug/ml. After statistical analysis, P>0.05, indicating that the overalldifference between the three groups was not statistically significant. BF value0f the before-after group before and after the treatment were40.971ml/min/100g、21.809ml/min/100g、33.442ml/min/100g，respectively. Thereis an increasing trend, but by statistical analysis, the difference was notstatistically significant (P>0.05). Meanwhile BF values of the Endo+TP groupbefore and after the treatment were42.105ml/min/100g、31.663ml/min/100g、27.305ml/min/100g, respectively. The BF valuesincreased after treatment, and the difference was statistically significant(P<0.05). BF values of the control group before and after treatment were:44.828ml/min/100g、33.972ml/min/100g、25.464ml/min/100g, respectively.The difference was not statistically significant (P>0.05). BF values of thethree groups after treatment were not statistically significant comparisons(P>0.05). BV has value of the before-after group before and after were3.820ml/100g、2.203ml/100g、14.658ml/100g, respectively. The BV valuesincreased after treatment, by statistical analysis, the difference was statisticallysignificant (P<0.05). Meanwhile BV values of Endo+TP group before andafter the treatment were4.471ml/100g、4.164ml/100g、2.27ml/100g, respectively.The difference was not statistically significant (P>0.05). BVvalues of the control group before and after treatment were5.336ml/100g、4.570ml/100g、3.956ml/100g,respectively.The BV values reduced aftertreatment than before,the difference was statistically significant (P<0.05).After treatment,the three groups of BV value were no statistical significance(P>0.05). MTT values of the before-after group before and after the treatmentwere12.725s、12.233s、16.506s, respectively.The MTT values reduced aftertreatment than before, by statistical analysis, the difference was statisticallysignificant(P<0.05). Meanwhile MTT values of the Endo+TP group beforeand after the treatment were:10.825、11.849s、8.562s, respectively.Thedifference was not statistically significant (P>0.05). The MTT values ofcontrol group before and after treatment were10.529s、9.94s、11.971s,respectively.The difference was not statistically significant (P>0.05). MTTvalue after three treatment groups was statistically significant (P>0.05). PSvalues of the before-after group after treatment were8.57ml/min/100g、18.12ml/min/100g, respectively.The PS values increased after treatment than beforetreatment, but the difference was not statistically significant (P>0.05).Meanwhile PS values of the Endo+TP group before and after the treatmentwere6.89ml/min/100g、11.25ml/min/100g, respectively. The difference wasnot statistically significant (P>0.05). PS values of the control group before andafter treatment were9.859ml/min/100g、8.929ml/min/100g、15.218ml/min/100g, respectively. The difference was not statistically significant (P>0.05). The difference of the PS values after treatment of the three groupswas not statistically significant (P>0.05). Conclusion: Endostar does notincrease the toxicity of chemotherapy drugs when used in combination withchemotherapy drugs, and the treating patients were well tolerated. Theefficacy of recombinant human endostatin in different administrationsequences combination with paclitaxel and cisplatin treatment of non-smallcell lung cancer was no significant difference in the need to expand the samplesize for verification. CT perfusion can be observed the BV values decreased inthe before-after group after treatment, suggesting that this joint approachallows the tumor tissue increased capillary leakage of blood cancerchemotherapy drugs to penetrate more easily organization, a greater degree ofkill tumor cells, improve the efficacy.