Phase ? Study Of High-dose Pemetrexed Plus Cisplatin In The Treatment Of Patients With Brain Metastases From Lung Adenocarcinoma (Wild Type)

Background and Purpose: Lung cancer is the leading cause of cancer-related deaths in the world and mortality has been increasing year by year.With the increase of awareness of tumor molecular biology,driven genes of lung cancer such as EGFR,ALK have been found.Targeted therapy has developed rapidly and become a hot spot in clinical research and application.The previous researches showed that the survival of patients with EGFR-mutated NSCLC who receive EGFR-TKIs are significantly greater than those of patients who receive chemotherapy.However,the mutation of EGFR is limited.EGFR mutations accounted for 21% in the Caucasian population while approximately 40%-60% in the Asian population.This means that the EGFR mutation status are wild type in 30%-40% patients with NSCLC.NCCN guidelines suggested that patients with EGFR mutation positive should be treated with TKIs,and EGFR wild type could be treated with chemotherapy.Lung adenocarcinoma is one of the most common pathological type of lung cancer,and the incidence of distant metastasis is higher,and usually in the early stage.Brain is one of the most common metastasis sites.About 10% of patients with NSCLC are diagnosed with brain metastasis at the time of diagnosis,and about 40%of patients with NSCLC are found brain metastasis in the later treatment.When surgery or radio-surgery are not possible,whole brain radiotherapy(WBRT),Sterol Radiation Surgery(SRS)and WBRT+SRS are the standard treatments,with a cerebral response rate of approximately 30%.Pemetrexed-based chemotherapy presented about 40% response rate on brain lesions of NSCLC with brain metastases.In order to explore the optimal treatment for patients with lung adenocarcinoma(wild type)with brain metastases,we selected high-dose pemetrexed plus cisplatin chemotherapy to study the efficacy and safety of the first-line treatment.Methods: This trial assessed the efficacy and safety of high-dose pemetrexed plus cisplatin in lung adenocarcinoma(wild type)with brain metastases(mulifocality(?3),special type(?2cm))after WBRT.Thirty two patients with KPS?70 were enrolled.Patients of NSCLC with brain metastases were eligible for WBRT whichwas administered at 30Gy/10 f.Thereafter,high-dose pemetrexed plus cisplatin was given up to six cycles.Primary end point was objective response rate(RR)and progression free survival(PFS)on lung adenocarcinoma(wild type)with brain metastases(mulifocality(?3),special type(?2cm)).Secondary end points included extracerebral and overall RR,safety profile and survival.Results: The objective cerebral RR(complete and partial response)was 68.8 %(22 of 32 patients).Extracerebral and globe RR was 37.5% and 31.3 %,respectively.The DCR of the whole patients was 84.4%.The median progression free survival(PFS)of lung adenocarcinoma(wild type)with brain metastases(mulifocality(?3),special type(?2cm))was 13.6 months,and median overall survival(OS)was19.1months.The incidence of adverse reactions in patients was within the controllable range.Conclusions: This modality of treatment appears to a better efficacy and a good safety of lung adenocarcinoma(wild type)with brain metastases(mulifocality(?3),special type(?2cm))who cannot treated surgically,as well as extracerebral.It can be used as an effective treatment in clinical.