Endocrine therapy is the most important systemic therapy for hormone receptor positive breast cancer.However,intrinsic or acquired resistance to endocrine therapy is a challenge currently.Crosstalk between estrogen receptor pathway and other pathway is considered to be one of the underlying mechanisms.Progress has been made in reversing resistance by blocking signaling through pathways such as the phosphoinositide 3-kinasesprotein kinase B-mammalian target of rapamycin and epidermal growth factor receptor pathway.

The cytotoxic agents pemetrexed and docetaxel and the epidermal growth factor receptor (EGFR)tyrosine kinase inhibitors(TKIs)erlotinib and gefitinib are standard second-line therapies for non-small cell lung cancer. For patients without the EGFR mutation,more and more evidence has suggested the superiority of chemotherapy over targeted therapy. Adding targeted agents to standard second-line treatment is an trend of exploration,but without promising results nowadays. Crizotinib,targeting at anaplastic lymphoma kinase,has been shown excellent efficacy for second-line therapy in non-small cell lung cancer.

Objective To observe the effect of high-dose leucovorin(LV)plus 5-fluorouracil(5-Fu)for 48hours infusion in combination with cisplatin(DDP)in treatment of advanced esophageal cancer.Methods Pathological diagnosis of esophageal cancer 60 cases were randomly divided into treatment group of 30 patients,using DDP 25mg/m2 intravenous infusion 30 minutes,d1～3,LV 200mg/m2 intravenous infusion 2 hours,5-Fu 0.5 intravenous injection 10 minutes,and 5-Fu 2.5/m2,continuous infusion with the infusion pump for 48 hours every 21 days,2 cycles of assessment of efficacy.Control group of 30 patients,using DDP 25mg/m2 intravenous infusion 30 minutes,d1～3,LV 60mg/m2 intravenously two hours,d1～5,5-Fu 500mg/m2 intravenously 8 hours every 21 days,2 cycles of assessment of efficacy.Results Short-term effect,treatment group,complete remission(CR)1 patient and partial remission(PR)15 cases,stable(SD)9 cases,progress(PD)5 cases,the total effective rate of CR + PR53.3％(16/30).Control group,PR 11 patients,SD 11 cases,PD 8 cases,no cases of PR,the total effective rate 36.7 ％(11/30).Nausea,vomiting,oral mucositis,bone marrow suppression,diarrhea and hair loss were the main adverse reactions.Two groups are able to withstand,without any Ⅳ toxicities,myelosuppression was significant in control group than the treatment group.Conclusion High-dose LV + 5-Fu 48 hours infusion combined platinum-term efficacy in treatment of advanced esophageal cancer compared with conventional DF program is good,less adverse reactions,should further expand the study.