Erlotinib as a salvage treatment for patients with advanced non-small cell lung cancer after failure of gefitinib treatment

Background Several clinical trials showed that erlotinib was effective after the failure of gefitinib in advanced non-small cell lung cancer （NSCLC）. The aim of this study was to evaluate the feasibility of erlotinib treatment after the failure of gefitinib based on the data from our hospital. Methods The clinical data of 20 patients with advanced NSCLC who were admitted to Shanghai Chest Hospital from August 2007 to December 2008 were retrospectively analyzed. All of the patients were given erlotinib treatment after the failure of gefitinib. Survival analysis was made by Kaplan-Meier method. The Cox regression model was performed to analyze the relationship between the influential factors and the erlotinib progression-free survival （PFS）. Results Five patients had a partial response （PR）, nine patients had stable disease （SD） and six patients had progressive disease （PD） with gefitinib treatment. The median PFS was 277 days （95% CI 0-566）. No patient had a PR, seven had SD and fourteen PD with the erlotinib therapy. The median PFS was 31 days （95% CI 9.1-52.9）. The response rate （RR） was 0, and the disease control rate （DCR） was 35% （7/20）. Cox regression analysis demonstrated that sex （P=0.96）, age （P=0.89）, smoking history （P=0.78）, performance status （PS） （P=0.98）, gefitinib efficacy （P=-0.90） and whether chemotherapy was applied between using the two drugs （P=-0.45） had no significant correlation with erlotinib PFS. Fifteen patients had epidermal growth factor receptor （EGFR） mutation status determined. There were five cases got SD with the erlotinib treatment in ten mutation negative （wild-type） patients. No SD was recorded in the five mutation positive patients. Conclusions The efficacy of erlotinib treatment after gefitinib failure was limited. However, the patients who are EGFR mutation negative can probably benefit from erlotinib treatment after gefitinib failure.

Pemetrexed monotherapy versus pemetrexed plus platinum combination as second-line treatment for advanced non-small cell lung cancer

Background Pemetrexed is a novel folic acid antagonist with multiple targets, which has been widely used in the treatment of non-small cell lung cancer （NSCLC）. The objective of this study was to compare the effects and toxicities in NSCLC patients treated with pemetrexed monotherapy versus pemetrexed plus a platinum combination agent, so as to provide a basis for standard second-line chemotherapy. Methods The clinical data of 52 patients with NSCLC who were admitted to Shanghai Chest Hospital from August 2006 to October 2008 were retrospectively analyzed. Ten of the 52 patients received pemetrexed monotherapy, and the other 42 patients received the pemetrexed plus platinum regimen. The primary end point was overall survival （OS）. The progression-free survival time （PFS） was analyzed and the effects and toxicities were assessed. Survival analysis was evaluated by Kaplan-Meier method. Single factor analysis and the COX regression model were done to analyze the relationship between the influential factors and the prognosis of disease. The elderly patients （〉60 years old） were analyzed separately as a subgroup. Results No statistically significant increase in OS （x^2=0.09, P=0.76）, PFS （x^2=0.15, P=0.70）, disease control rate （DCR） （x^2=0.06, P=0.81） or 1-year survival rate （x^2=0.33, P=0.57） was found between the two regimens. Single factor analysis showed that the factors including surgery history, PS score before treatment, clinical stage, and response to second-line treatment influenced the prognosis of NSCLC （all P 〈0.05）. COX regression analysis demonstrated that surgery history （P=-0.041） and performance status （PS） score before treatment （P=0.043） may be associated with survival. The toxicity of the two regimens was similar. In the subgroup of elderly patients, no significant difference in OS （x^2=0.01, P=0.94）, PFS （x^2=0.14, P=0.70）, DCR （x^2=0.004, P=-0.95）, or 1-year survival rate （x^2=0.03, P=0.87） was found between the two regimens. The toxicity of combination therapy was significantly higher in terms of hematologic （x^2=g.95, P=-0.01） and gastrointestinal adverse events （x^2=7.66, P=0.03）. Conclusions There is no significant difference in survival or side effects between these two regimens. For elderly patients （〉60）, pemetrexed monotherapy shows similar efficacy and a better safety profile when compared with pemetrexed combination therapy.

Isoliquiritigenin induces HMOX1 and GPX4-mediated ferroptosis in gallbladder cancer cells

Background:Gallbladder cancer(GBC)is the most common malignant tumor of biliary tract.Isoliquiritigenin(ISL)is a natural compound with chalcone structure extracted from the roots of licorice and other plants.Relevant studies have shown that ISL has a strong anti-tumor ability in various types of tumors.However,the research of ISL against GBC has not been reported,which needs to be further investigated.Methods:The effects of ISL against GBC cells in vitro and in vivo were characterized by cytotoxicity test,RNA-sequencing,quantitative real-time polymerase chain reaction,reactive oxygen species(ROS)detection,lipid peroxidation detection,ferrous ion detection,glutathione disulphide/glutathione(GSSG/GSH)detection,lentivirus transfection,nude mice tumorigenesis experiment and immunohistochemistry.Results:ISL significantly inhibited the proliferation of GBC cells in vitro.The results of transcriptome sequencing and bioinformatics analysis showed that ferroptosis was the main pathway of ISL inhibiting the proliferation of GBC,and HMOX1 and GPX4 were the key molecules of ISL-induced ferroptosis.Knockdown of HMOX1 or overexpression of GPX4 can reduce the sensitivity of GBC cells to ISL-induced ferroptosis and significantly restore the viability of GBC cells.Moreover,ISL significantly reversed the iron content,ROS level,lipid peroxidation level and GSSG/GSH ratio of GBC cells.Finally,ISL significantly inhibited the growth of GBC in vivo and regulated the ferroptosis of GBC by mediating HMOX1 and GPX4.Conclusion:ISL induced ferroptosis in GBC mainly by activating p62-Keap1-Nrf2-HMOX1 signaling pathway and downregulating GPX4 in vitro and in vivo.This evidence may provide a new direction for the treatment of GBC.