Clinical Research About The Protection Of Shenqi Injection Of The Heart To A New Recombinant Human Endostatin Combined With Chemotherapy

Background:Most advanced cancer need to be treated with drugs,espasially chemo-combined therapy.More and more evidences show thatanti-angiogenesis drugs combined with chemotherapy drugs can improve the therapeutic effects, bring with the survival benefits.TheⅡ-Ⅲphase clinical trials in patients with advanced non-small cell lung cancer patients have confirmed that the new recombinant human endostatin(new rh-endostatin or Endostar)combined with NP(NVB+DDP)chemotherapy can improve tumor response rate(RR)and clinical benefit rate(CBR),prolong the median time to disease progression(TTP), improve the quality of life(QOL)and overall survival(OS),and the adverse reactions can be tolerated.As a broad-spectrum anti-angiogenesis drug,the greatest advantage of endostar is that it has the wider indications,without specific pathology requirements to tumor.It has also been reported that the treatment of endostar combined with chemotherapy showed a certain efficacy in other advanced tumors. With the continuous expansion of indications,the security of Endostar treatment becomes particularly important.In the United States,one patient with coronary heart disease suffered from myocardial infarction during the phaseⅡclinical trial of recombinant human endostatin.In China,the results ofⅠ-Ⅲphase clinical trials of endostar shows that,the dose limited talxity(DLT)of endostar in body is related to a variety of cardiac adverse reactions,with the rate of 6.38%~ 13.2%.And in phaseⅡclinical trial,Ⅲdegree cardiac adverse reactions have taken place in one patient in Group 30 mg/m2.Shenqi injection is composed of Codonopsis pilosula and astragali.A large number of pre-clinical and clinical studies have proved that,Shenqi injection has the functions of killing tumor cells synergistically,protecting bone marrow,enhancing the body immunity,and reducing cardiac toxicity caused by chemotherapy.It has also been proved being a safty drug in clinical treatment.At present,there is no research about the protection of the heart in treatment of endostar combined with chemotherapy be reported,especially the related research of traditional Chinese medicine.It shows certain clinical significance to investigate whether Shenqi injection can reduce the cardiac adverse reaction and whether it has a synergistic anti-tumor function in treatment of endostar combined with chemotherapy,Purpose:Choose the patients with advanced cancer(mainly non-small cell lung cancer)as research object,observe the heart protective effect and synergistic effect of Shenqi injection during combination chemotherapy with endostar.Patients and Method:Using prospective case-control study,48 patients diagnosed by histopathology with malignant tumor ofⅢorⅣstage from our hospital and the First Hospital of the Guangzhou University of Chinese Medicine during March,2007 to February,2008,were divided into two groups according to with(Group A)or without(Group B)Shenqi during endostar combination chemotherapy.Myocardial enzymogram,electrocardiogram,left ventricular ejection fraction(LVEF),plasma troponinⅠ(troponinⅠ),cardiovascular adverse reactions and the quality of life(QOL),the recent therapeutic effect(CR,PR,SD,PD),time to disease progression(TTP)were evaluated before and after the treatment。SPSS software was used for statistical analysis.Result:1,48 patients can evaluate the cardiac toxicity.The LVEF,serum myocardial enzymogram,serum troponinⅠare all in the normal range before treatment,and the equilibrium between two groups is belance.2,LVEF of Group B patients is decreased after treatment,while Group A increased,the diversity has statistical significance(P=0.0265).And the LVEF of both Groups are in the nomal range.The diversity of LVEF between before and after treatment within Group A or within Croup B has no significant difference.It is observed a certain increase of myocardial enzymogram in both groups after treatment,with higher occurrence in Group B,but without statistical significant difference.Certain electro -cardiogram abnormality after treatment is observed in both groups,with higher occurrence rate in Group B(41.66%).The diversity in Group B between before and after treatment is significantly significant(P＜0.05).But the difference in group A between before and after treatment,and the difference between the two groups after treatment both have no significant significancy(P＞0.05).Both groups have a certain cardiovascular adverse reactions,with slightly higher rate in Group B,but no significant difference(P＞0.05).Both groups have no obvious cardiac dysfunction.It is observed a certain incidence of deep vein thrombosis in both groups(P＞0.05).It seems to show higher adverse reaction in patients who ever used epidermal growth factor inhibitors.3,The quality of life in Group A has raised after therapy,with statistical significance(P＜0.05).The quality of life in Group B seems to show declining trend after treatment,but without statistical significance(P＞0.05).The diversity of quality of life between Group A and B both have no obvious difference before or after treatment.4.The study did not show that Shenqi injection can influence the recent therapeutic effects and TTP with using in endostar - chemotherapy.Of 38 cases with non-small cell lung cancer,RR of treatment group vs control group was 35%vs 27.78%(P＞0.05),CBR of treatment group vs control group was 70% vs66.67%(P＞0.05).The median TTP were 98 days and 61 days respectively(P＞0.05). It also observed that endostar - chemotherapy have certain effect on other tumors.And because the number of the cases is too small,it can not reflect the overall effect.Conclusion:1.Endostar combined chemotherapy caused certain cardiotoxity,which is related to Endostar.Shenqi injection has certain heart protection effects against Endostar combined chemotherapy,and improved the life quality without obvious influence on curative effects.When no cardiac muscle toxic drugs were choosed in Endostar combined chemotherapy with certain indication,and a recommended dose was applied,cardiovascular adverse effects of patients were less serious,and the heart protection effects of Shenqi injection under this situation was not so obvious.2.Myocardial damage monitoring index should be a routine detection when Endostar is used in combined chemotherapy,and further observation of heat adverse effects should be carried on. 3.Further safety evaluation of usage of Endostar,Endostar combined other myocardia toxic chemotherapy drugs,and Endostar combined anti-epiderm growth factor chemotherapy in a long term should be studied.