The Clinical Observation Of Zoledronic Acid In Combin-ation With Cytotoxic Drug In Patients With High Level NTX Stage â…¢B Or Stage â…£ Non-Small Cell Lung Cancer

BackgroundLung cancer, one of the dominate malignant tumors, is the frequent reasoncaused cancer related death, which has an increasing incidence and mortality in recentyears. Depending on biological behavior, lung cancer is divided into small cell lungcancer (SCLC) and non-small cell lung caner (NSCLC).80%of total lung cancerpatients are NSCLC patients. And most patients are in advanced stage usually whendiagnosed without any chance for radical operation. Up to now, there has been nobreakthrough for chemotherapy or combination of chemotherapy and radiotherapy forⅢB/Ⅳstage NSCLC cases. In decade, although combination of third-generationcytotoxic drug and platinum has improved the survival, the prognosis of advancedNSCLC is still poor with a20%-40%effective power for first-line chemotherapy and8-12months median survival. So searching new anti-cancer drugs becomes theclinical research hotspot. Zoledronic acid, which is the third nitrogen bisphosphonates,can induce direct and indirect antitumor activities through inhibiting thepyrophosphate synthase activity in the mevalonate pathway. Preclinical studies oflung cancer, breast cancer etc. confirm that zoledronic acid has a certain synergycombining with cytotoxic drugs and some targeted drugs. And now this conclusion is being verified by clinical trials.ObjectiveOur research is aimed at observing the efficiency and safety of zoledronic acidcombining with cytotoxic drug in patients with high level NTX stage IIIB or stage IVnon-small cell lung cancer. In effect analysis, we estimate oncosis depending oniconography，and detect the level of NTX. In subset analysis, we analyze the clinicalfactors including sex, age, histology, encroachment to look for the factors affectingNTX basic counts. In correlation analysis, we analyze the correlation between NTXlevel and treatment effectiveness respectively.MethodsWe choose patients relying on NTX，which is over50nmol/mmolBCE, dividethose who enrolled in our research into two groups，control group with chemotherapyand trial group with chemotherapy and zoledronic acid. Patients in control group wereaccepted the third regimen with cisplatin with a21-day cycle. And the trial groupwere accepted the third regimen with cisplatin followed by4mg zoledronic acid after24hours with a21-day cycle. Thirty three ⅢB/Ⅳ stage NSCLC patients treated atShandong Tumor Hospital from September2010to December2011were included inthis study. We collect the second urine to detect NTX level using enzyme linkedimmunosorbent assay before treatment, after the second cycle, after the fourth cycle,respectively. MCT enhancement scanning is used to estimate therapeutic effectvariation before treatment，after the second cycles and after the fourth cycles.According to the result, we analyze the relationship between NTX level andtherapeutic effect. Effect is evaluated according to RECIST standard with effectivepower (CR+PR) and clinical benefit (CR+PR+SD). Data processing is performedusing SPSS16.0medical statistical analysis, and P <0.05is defined as there isstatistical significance in difference. Results1NTX levels comparison between the control group and the trial group: there isno statistical significance in differences of NTX levels between control group and trialgroup before treatment. And the result is identical after2cycles. But after4cycles theNTX levels of control group and trial group is60.51±3.09nmol/mmolBCE and48.30±2.31nmol/mmolBCE respectively. There is statistical significance indifferences.2The influence of clinical factors to uNTX levels: we analyzed clinical factorsincluding sex, age, histology, encroachment. Among them, no factors had statisticalsignificance (P＞0.05).3Effect in the near future:20persons enrolled in control group and13enrolledin trial group.There were CR1(5.0%), PR5(25.0%), SD6(30%), PD8(40%) withRR30%and clinical benefit60%in control group. And there were CR0(0.0%), PR6(46.2%), SD3(23.1%), PD4(30.8%) with RR46.2%and clinical benefit69.3%intrial group. there is no statistical significance in differences resectively of RR and therate of clinical benefit.4The change of NTX levels: there is no significant difference of uNTX levelsbefore treatment, after2cycles and4cycles in control group while the result is notconsistent with the trial group.5NTX levels comparison between clinical effect patients and clinical benefitpatients in control group and the trial group: ZA combining with chemotherapy candecrease NTX levels significantly in clinical effect patients and in clinical benefitpatients. And the result of control group is on the contrary.There are significant deference between clinical benefit patients and PD patientswith45.79±1.61nmol/mmolBCE and56.67±7.34nmol/mmolBCE respectively intiral group.6TTP comparison between the control group and the trial group: the TTP ofcontrol group and trial group is4.0months and6.3months. And the bone-TTP ofcontrol group and trial group is3.5months and6.3months. Both of them have nodifference.7Correlation between NTX level and therapeutic effect: there is no correlation between therapeutic effect and NTX levels.Conclusions1There is on elevation of RR and clinical benefit rate to ⅢB/Ⅳ stage NSCLCdepending on ZA combining with chemotherapy.2ZA combining with chemotherapy can decrease NTX levels whilechemotherapy can not.3The clinical factors including sex, age, histology, encroachment can notinfluence NTX levels.4ZA combining with chemotherapy can decrease NTX levels in clinical effectpatients and in clinical benefit patients. The decrease of clinical benefit patients aremore than PD patients.5there is no extension of TTP and bone-TTP in combination chemotherapygroup.6No more adverse reaction events are increased in combination chemotherapygroup than control group.7there is no relationship between therapeutic effect and NTX levels.