| Purpose and Background: Lung cancer is currently the world ’shighest incidence of malignancy, which has become the leading cause ofcancer death.The poor prognosis is mainly due to local recurrence anddistant metastasis. With the increase of the incidence of lungcancer,prolonged survival and improved diagnostic techniques, thedetection rate of brain metastasis is rising. Because of the poor prognosisof brain metastases, the median survival is3.1-12.0months. Treatmentmethods of brain metastases from lung cancer include whole brainradiotherapy, chemotherapy, radiotherapy, surgical resection andsymptomatic treatment. With the extensive use of small molecule tyrosinekinase inhibitor(erlotinib), scholars began to explore the response of thesedrugs combining with radiotherapy. We retrospectively analyzed67patients sufferred from non-small cell lung cancer with brain metastasisin our department of oncology from2009to2012, and mainly observedin the short-term effect, survival analysis and toxicity.Methods: We studied67NSCLC patients diagnosed by pathologyor cytology between January2009and May2012at China-Japan UnionHospital Of Jilin University, divided into the treatment group (erlotinibcombined with whole brain radiation therapy) and the controlgroup(whole brain radiation therapy alone).32cases in the treatmentgroup were all adenocarcinoma, including10males and22females,whose median age was54years.15cases of EGFR mutation positive (exon19mutations in12cases, exon21in3cases), negative in7cases,the mutational status unknown in10cases. According to lung cancerTNM staging system of International Associaton for the Study of LungCancer(IASLC) version7.0, all cases were stage IV. PS score (ECOG)were0to3. Expected survival time was more than3months. All patientshad no obvious heart failure and respiratory failure. Enrolled patientsreceived whole brain radiotherapy, DT (3000-3600) cGy/(10-12) F.From onset of radiotherapy patients started using erlotinib150mg, PO,Qd until2months after the completion of radiation. In the control group,32cases were all adenocarcinoma, including16males and19females,whose median age was63years. EGFR mutation status was unknown.All cases underwent whole brain radiotherapy. The cases of control groupregularly hospitalized and reviewed, and cases in treatment groupbimonthly were in outpatient follow-up or hospitalized follow-up. Thefollow-up included blood count, blood chemistry, tumor markers, chestCT, head CT or head MR and adverse drug reactions.SPSS19.0softwarewas applied for survival analysis with Kaplan-Meier method andcategorical data with chi-square test. P <0.05was considered statisticallysignificant.Results: In the treatment group, complete remission (CR) in4cases(12.5%), partial remission (PR) in14cases (43.8%), disease stability (SD)in12cases (43.8%) and progressive disease (PD) in2cases (6.3%).Objective response rate (ORR)(CR+PR) was56.3%(18/32), diseasecontrol rate (DCR)(CR+PR+SD) was93.8%(30/32). In the control group,complete remission (CR) in1case(2.9%), partial remission(PR) in5cases(14.3%), disease stability (SD) in17cases(48.6%) and diseaseprogression (PD)12cases(34.3%). Objective response rate(ORR)(CR+PR) was17.1%(6/35), disease control rate (DCR)(CR+PR+SD) was65.7%(23/35). ORR(CR+PR) and DCR (CR+PR+SD) of thetreatment group were significantly higher than the control group. ORRwas56.3%and17.1%, respectively(P=0.001); DCR was93.8%and65.7%, respectively (P=0.005). Survival:18cases survived after1-yearfollowed-up in treatment group,14cases without disease progression.11cases survived after1-year followed-up in control group,7cases withoutdisease progression.1-year survival rate of the treatment group was higherthan that of the control group, with56.3%(18/32) and31.4%(11/35)respectively(P<0.05);1-year progression-free survival rate of thetreatment group was higher than the control group, with43.8%(14/32)and20%(7/35) respectively (P=0.036). The median OS of control groupwas7.5months and the median OS of the treatment group was13.0months; The median PFS of control group was5.5months and thetreatment group was10.0months. Toxicity: In the treatment group, themain adverse events were rash and diarrhea. Rash rate was34.4%(11/32),I-II grade accounting for28.1%(9/32), III grade accounting for6.25%(2/32).Diarrhea rate was37.5%(12/32), I grade diarrhea incidencerate was25.0%(8/32), the grade II was12.5%(4/32). I grade leukocytereduction was6.25%(2/32), and no other hematologic toxicity occurred.Anorexia incidence rate was9.4%(3/32). Headache, nausea, vomiting andother symptoms of increased intracranial pressure rate was31.3%(10/32).In the control group, the main side effects were headache, nauseaand vomiting, the incidence was37.1%(13/35).5.71%(2/35) cases withI grade leukocyte reduction; no other hematologic toxicity; no rash anddiarrhea occurred. Cases in both groups had no nephrotoxicity,neurotoxicity, and no treatment-related deaths. Conclusion:1.In the treatment of non-small cell lung cancer with brainmetastases, the treatment response rate of erlotinib combined with wholebrain radiation therapy group was significantly higher than the controlgroup, and median PFS and median OS were significantly longer.2.The side effects of erlotinib were mild, which ensured thesustainability of the combination therapy.3.Erlotinib combined with whole brain radiation therapy isrecommended for the treatment of non-small cell lung cancer patientswith brain metastases, especially for EGFR mutation-positive patients. |
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