Clinical Research Of The Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor In Maintenance Therapy Advanced Non-small Cell Lung Cancer

Background and purpose:Lung cancer is currently the world ’s highest incidence of malignancy, hasbecome the leading cause of cancer death. Because of insidious onset, nospecific symptoms, most of patients losing operation cure chance,5yearssurvival rate is5%～10%. Although cluding platinum of double medicinechemotherapy remains the first line to standard treatment regimens of advancednon small cell lung cancer (NSCLC), but reaching its effect platform. Inrecent years, epidermal growth factor receptor tyrosine kinase inhibitor（EGFR-TKI) in treating advanced NSCLC has achieved remarkable effect,has become the first-line therapy to EGFR mutation of advanced non small celllung cancer. For the EGFR mutation of advanced NSCLC maintenancetreatment, a number of large-scale clinical trials to support to use EGFR-TKIthan supportive therapy,because of PFS was significantly prolonged ofEGFR-TKI team. Becase of defferent mechanisms, lower toxicity and sideeffects, better tolerance,EGFR-TKI is the ideal drug for maintence. The thesisaims to retrospectively analyzed EGFR-TKI and chemotherapeutic drug’sinclinical effects, the progression free survival and toxicity in maintenancetherapy for EGFR mutation of advanced NSCLC.Method：We studied38patients in advanced non small cell lung cancer, diagnosedbetween Janunary2008and March2012at China-Japan Union Hospital OfJilin University, including5males,33females, the median age was58years old.Adenocarcinoma in35cases, adenosquanosus carcinoma in2cases, squamous carcinoma in1cases. EGFR positive. According to the seventh edition LungCancer TNM staging system for cliniccal stage,IIIB stage are6cases, IV stageare32cases. The lesion could be estimated through the chest CT. All patientswith Karnofsky score≥80. Estamating the survival period over3months. Allpatients had no obvious pulmonary emphysema and respiratory failure.22patients were divided into therapeutic group and16patients were divided intocomparison group.Therapeutic group cluded5cases of erlotinib therapy,150mgeveryday,2h postprandia loral.17cases of gefitinib250mg every day, oral.Comparison group16case received single agent chemotherapy, including8cases of pemetrexed,4cases of gemcitabine,4cases of docetaxel. Usage:pemetrexed500mg/m2, on day1, every21days as a cycle, folic acid tablets400ug/d were taken from a week before pemetrexed was administered until21days after pemetrexed last used. A week before pemetrexed, VitB121000ugwas given by intramuscular injection and repeatd every three cycles.Theprevious day, the same day and the second day, dexamethasone was given4mgevery time,two times one day. Gemcitabine1000mg/m2by intravenousinfusion on the first and eighth day, every21days as a cycle. Docetaxel75/m2by intravenous infusion on the first day,every21days as a cycle, the previousday and the second day dexamethasone was given10mg, the same day30minutes before chemotherapy10mg dexamethasone was intravenous infusion.Estimateing the chest lesion by chest CT for every month. We quantified theseand used Х2to test the count data of clinical indicators, the progression freesurvival rate by log-rank test, SPSS17.0statistics software to drawKaplan-Meier disease progression free survival.Result：Efficacy: The therapeutic group: complete response(CR) is3(13.6%),partial response(PR) is12(54.5%), stable disease(SD) is5(22.7%),progressivedisease(PD) is2(9.1%),response rate(RR) is68.2%, disease control rate(DCR) is90.9%.The comparison group: complete response(CR) is2(12.5%), partialresponse(PR) is6(37.5%), stable disease(SD) is5(31.25%), progressivedisease(PD) is3(18.8%), response rate(RR) is50%, disease control rate(DCR)is81.3%. One years survival rate of81.8%(18/22) vs68.8%(11/16), two yearssurvival rate of63.3%(14/22) vs31.2%(5/16).The therapeutic group andcomparison group of PFS were respectively11.4months and5.0months. Twogroups of PFS, two years survival rate were significant statistically.CR,PR,SD,PD,RR,DCR,one year survival rates were not significant statistically.Side effects: the therapeutic group: the main side effect was rash and diarrhea.The rash rate was41%(9/22), Ⅰ～Ⅱgrade account for31.8%(7/22), Ⅲgradeaccount for9%(2/22). Diarrhea rate was27.3%(6/22)：Ⅰgrade diarrhea accountfor18.2%(4/22)，Ⅱgrade account for9.1%（2/22）.Ⅰgrade leucocyte reductionaccount for4.5%(1/22), no other hematological toxicity. Anorexia incidencewas4.5%(1/22), no nausea, vomiting. The comparisom group:the main sideeffects were hematologic toxicity. Mild bone marrow suppression rate was50%(8/16)：I grade leukocyte reduction31.3%（5/16），Ⅱgrade account for12.5%(2/16), Ⅰgrade thrombocytopenia account for6.25%(1/16), no otherhematological toxicity.Ⅰgrade nausea, vomiting account for18.8%(3/16).Ⅰgrade liver transaminase elevation account for6.25%(1/16), no Ⅱ～Ⅳgrade transaminase elevation. The two groups had no nephrotoxicity,neurotoxicity, no treatment related deaths.Conclusion:1. In the maintenance treatment of advanced non-small cell lung cancerwith EGFR positive, PFS and Two Years Survival Rate have significantstatistically difference.(PFS11.4months vs5.0months,P＜0.01. Two YearsSurvival Rate63.3%vs31.2%, P＜0.05)2.The EGFR-TKI side effects was mild, so guarantee the sustained treatment of persistent.3.EGFR-TKI can be used for maintenance therapy in advanced NSCLCwith EGFR positive.