A Study On Relation Of The Level Of CECs And Efficacy Of NP Regimen With Endostatin In Advanced Nsclc

BackgroundLung cancer is the most frequently diagnosed cancer in developed countries and in some big cities in China. Over the past several decades, there has been a fairly steady and large increase in the incidence of the disease. More than 80% of them are non-small cell lung cancers. And about 80% of patients given the diagnosis of NSCLC belong to advanced disease. For these patients with stage-Ill or stage-IV disease, chemotherapy plays a key role in combined-modality treatment of NSCLC. But drug resistance in lung cancer is very common. Folkman's theory was first argued in 1970's that neoplasms depend on the formation of new blood vessels (angiogenesis) for continued growth and metastatic spread. Recently, several naturally occurring angiogenesis inhibitors have been identified. The most potent inhibitor appears to be endostatin discovered by O'Reilly. So antiangiogenic treatment is one of the most promising antitumor strategies. This approach aims to suppress metastatic outgrowth by inhibiting the formation of a tumor-induced vascular network. So whether thenumber of CECs(circulating endothelial cells) is influenced by anticancer treatment such as endostatin or chemotherapy has been argued in recent years. ObjectiveTo evaluate the efficacy of chemotherapy combined with endostatin in treatment of non-small cell lung cancer(NSCLC) and to analyse the change and clinical values of circulating endothelial cells(CECS) in peripheral blood in patients with advanced NSCLC. Methods74 patients with advanced NSCLC were divided randomly into NP plus endostatin treatment group and NP contrast group, and CECs were measured by flow cytometry. (l)NP+endostatin(treatment group): NVB 25mg/m2 iv dl,5; DDP 30mg/m2 iv d2~4; Endostatin(YH—16)7.5 mg/m2 iv dl~14.NP(contrast group): NVB 25mg/m2 iv dl,5; DDP 30mg/m2 iv d2~4; NS 3.75ml iv dl~14. All patients were treated in two cycles(3 weeks a cycle). CECs were isolated and quantified from patients' whole blood by using an antibody directed against CD146, a pan-endothelial marker. The short term curative effects and TTP were evaluated after 2 cycles of treatment. Clinical Resonse Rate: CR+PR/total X 100 %, Clinical Benefit Rate: CR+PR+MR+SD/total X 100%.The whole experiment can be divided into three parts.Part I, Observing the efficacy and the change of CEC numbers of simple NP chemotherapy in treatment of advanced NSCLC, analyzing the correlative factors which influenced the curative effects.Part II, Observing the efficacy and the change of CEC numbers of NP chemotherapy combined with Endostatin in treatment of advanced NSCLC, analyzing the correlative factors which influenced the curative effects. Part III, Contrasting the efficacy and the change of CEC numbers of NP plus endostatin group and simple NP chemotherapy group in treatment of advancedNSCLC. Results1 Simple NP chemotherapy group, l)No correlation was found between clinical benefit rate and some data such as sex, history of operation, pathology and stage of disease; Benefit rate correlated with age, TTP and ACECs (=CECs before treatment—CECs after treatment). It showed that patients of lower age would be able to benefit from NP chemotherapy and patients benefiting from it would have a longer TTP and a higher ACECs. But patients with lower level of CK after treatment had a tendency to benefit from chemotherapy(P=0.055). 2)TTP had a strong correlation with benefit rate(P=0.001). There was no correlation between TTP and other data. 3)The number of CECs of all patients did not decrease after chemoptherapy(P=0.915). Patients in benefit had a little decrease in the number of CECs(P=0.237) while patients out of benefit had a tendency of increase in the number of CECs(P=0.056)2 NP chemotherapy plus Endostatin group, 1) No correlation was found betweenclinical benefit rate and some data such as sex, history of operation, pathology and stage of disease; Benefit rate correlated with TTP and ACECs (=CECs before treatment—CECs after treatment). 2)TTP had a strong correlation with benefit rate(P=0.000). It also had a negative correlation with the level of CK after treatment(r=-0.592, P=0.042). There was no correlation between TTP and other data. 3) The number of CECs of all patients decreased after chemoptherapy combined with Endostatin(P=0.001). Patients in benefit had a remarkable decrease in the number of CECs(P=0.000) while patients out of benefit did not decrease in the number of CECs(P=0.056).3 Treatment group and contrast group, l)contrast of base line: There was no marked difference in age, sex, history of operation, pathology and stage of disease between two groups. 2)contrast of benefit rate: There was a markeddifference(P=0.012). 3)contrast of response rate: There was no marked difference(P=0.176). 4)contrast of TTP: There was no marked difference(P=0.061). But when the cut-off of TTP was defined as >170 there was a marked difference between two groups. 5)contrast of CECs: There was no difference in the number of CECs before treatment(P=0.298); And there was no difference in the number of CECs after treatment(P=0.078); But there was marked difference in the number of ACECs (P=O.O33). 6)contrast of CK: There was no difference in the level of CK before treatment(P=0.223); And there was no difference in the level of CK after treatment(P=0.160); But there was marked difference in the level of ACK (P=0.034). 7)contrast of hemagram: There was no difference in the number of WBC, RBC and PLT between two groups.4 The usage of CECs in advanced NSCLC, l)In our study 74 patients' CECs were measued which confirmed the existence of CECs in cancer patients. 2)relation of CECs and efficacy: The number of CECs decreasd after NP chemotherapy combined with Edostatin (P=0.001) while it did not in simple NP chemotherapy group (P=0.915). The benefit rate and TTP of treatment group was superior to those of contrast group. It indicats that CECs not only plays an important role in neovascularization but also has a possible correlation with efficacy and prognosis. 3)relation of CECs and base line: There was no correlation between the level of CECs and data such as age, sex, history of operation, pathology and stage of disease. 4)correlation between CECs and CK: There was a correlation between CECs and CK before treatment(r=0.381, P=0.013) and after treatment(r=0.450, P=0.004); Considering the different management between two groups, the data were also divided into two groups. It showed that there was a correlation between CECs and CK in contrast group(r=0.668, P=0.009) while there was not in treatment group( r=0.214, P=O.294).Conclusions1 hi NP chemotherapy group Benefit Rate correlated with age, TTP and ACECs (=CECs before treatment—CECs after treatment). It showed that patients of lower age would be able to benefit from NP chemotherapy and patients benefiting from it would have a longer TTP and a higher ACECs. No correlation was found between Benefit Rate and other data; The number of CECs of all patients did not decrease after chemoptherapy. Patients in benefit had a little decrease in the number of CECs while patients out of benefit had a tendency of increase in the number of CECs.2 In NP chemotherapy plus Endostatin group Benefit Rate correlated with TTP and ACECs (=CECs before treatment—CECs after treatment). No correlation was found between Benefit Rate and other data. The number of CECs of all patients decreased after chemoptherapy combined with Endostatin. Patients in benefit had a remarkable decrease in the number of CECs while patients out of benefit did not decrease in the number of CECs.3 Benefit Rate and TTP of NP plus Endostatin treatment group were both superiorto those of NP contrast group, and the decrease of CECs and CK was higer in compined treatment group. There was no difference in the number of WBC, RBC and PLT between two groups.4 CECs can be detected in patients with advanced NSCLC. The number of CECs decreasd after NP chemotherapy combined with Edostatin while it did not in simple NP chemotherapy group.CECs not only plays an important role in neovascularization but also has a possible correlation with efficacy. There was no correlation between the level of CECs and data such as age, sex, history of operation, pathology and stage of disease. There was a correlation between CECs and CK before treatment ; And after treatment there was a correlation between CECs and CK in contrast group while there was not in treatment...