Lung cancer is the most widespread type of cancer and the primary cause of cancer-related death in the world.In this study,we aimed to analyze the cost-effectiveness of second-line chemotherapy strategies based on gem...Lung cancer is the most widespread type of cancer and the primary cause of cancer-related death in the world.In this study,we aimed to analyze the cost-effectiveness of second-line chemotherapy strategies based on gemcitabine,pemetrexed,and docetaxel for advanced non-squamous non-small cell lung cancer patients in China.A Markov model based on three states,progression-free survival,progressed survival and death,was constructed to simulate the progression of the disease in a 6-year horizon.Sensitivity analysis was performed to evaluate the robustness of the model.The primary outcome of the model was the incremental cost-effectiveness ratio at a willingness-to-pay threshold of 3×per capita GDP of China in 2018($29383).The baseline model results showed that the quality-adjusted life years over the course of the disease associated with second-line chemotherapy strategies were 0.233,0.417 and 0.272 for gemcitabine,pemetrexed and docetaxel,respectively,and the corresponding total costs were$5321.02,$12143.94,and$9479.42.Gemcitabine,pemetrexed and docetaxel resulted in the incremental cost-effectiveness ratios of$37081.09 and$106625.64 per quality-adjusted life year gained.The incremental cost-effectiveness ratio of pemetrexed and docetaxel compared with gemcitabine exceeded the willingness-to-pay threshold.One-way sensitivity analysis showed that the utility value of gemcitabine in the progressed survival state was the most influential parameter.展开更多
Multidrug resistance （MDR） of breast cancer is a major cause of failure in chemotherapy. In the present study, a distearoylphosphatidyl ethanolamine-polyethylene glycol-pemetrexed （DSPE-PEG2000-PMT） conjugate was ...Multidrug resistance （MDR） of breast cancer is a major cause of failure in chemotherapy. In the present study, a distearoylphosphatidyl ethanolamine-polyethylene glycol-pemetrexed （DSPE-PEG2000-PMT） conjugate was synthesized from DSPE-PEG2000-NH2 and pemetrexed, and targeted sunitinib plus vinorelbine liposomes were developed by modifying DSPE-PEG20o0-PMT onto the surface of liposomes to overcome the MDR of breast cancer. The synthesized DSPE-PEG2000-PMT was confirmed to be consistent with the target product by matrix-assisted laser desorption/ionization time of flight mass spectrometry （MALDI-TOF-MS）. The concentrations of sunitinib and vinorelbine were measured simultaneously by high performance liquid chromatography （HPLC）. The analysis was performed on an ODS column at 30℃ at a wavelength of 215 nm with the mobile phase consisting of acetonitrile, 0.05 M KH2PO4 （pH 3.5） and triethylamine （35：65：0.3, v/v/v）. The limits of detection for sunitinib and vinorelbine were 25 ng/mL and 5 ng/mL, respectively, and the limits of quantification for both drugs were 0.25μg/mL. Two drugs were linearly correlated in the range of 0.5-25.0 μg/mL. For varying types of liposomes, the encapsulation efficiencies were 〉90%; the particle sizes were approximately 90 nm, and zeta potentials were slightly negative. The inhibitory effects were evaluated in the resistant breast cancer MCF-7/Adr cells. The results revealed that targeted sunitinib plus vinorelbine liposomes exhibited the strongest inhibitory effect to the resistant MCF-7/Adr cells among the varying formulations. Targeted coumarin liposomes were used as a fluorescent probe to evaluate the targeting effect to resistant breast cancer MCF-7/Adr cells. The results demonstrated that the targeted coumarin liposomes displayed the highest cellular uptake compared to non-targeted formulations. In conclusion, the targeted sunitinib plus vinorelbine liposomes represented a novel type of nano-formulations, which could accumulate in the resistant breast cancer cells, thereby inhibiting proliferation of the resistant cancer cells. Accordingly, the targeted sunitinib plus vinorelbine liposomes may provide a new strategy for circumventing the drug resistance in the resistant breast cancer.展开更多
基金Startup Fund for Scientific Research,Fujian Medical University(Grant No.2018QH1091)。
文摘Lung cancer is the most widespread type of cancer and the primary cause of cancer-related death in the world.In this study,we aimed to analyze the cost-effectiveness of second-line chemotherapy strategies based on gemcitabine,pemetrexed,and docetaxel for advanced non-squamous non-small cell lung cancer patients in China.A Markov model based on three states,progression-free survival,progressed survival and death,was constructed to simulate the progression of the disease in a 6-year horizon.Sensitivity analysis was performed to evaluate the robustness of the model.The primary outcome of the model was the incremental cost-effectiveness ratio at a willingness-to-pay threshold of 3×per capita GDP of China in 2018($29383).The baseline model results showed that the quality-adjusted life years over the course of the disease associated with second-line chemotherapy strategies were 0.233,0.417 and 0.272 for gemcitabine,pemetrexed and docetaxel,respectively,and the corresponding total costs were$5321.02,$12143.94,and$9479.42.Gemcitabine,pemetrexed and docetaxel resulted in the incremental cost-effectiveness ratios of$37081.09 and$106625.64 per quality-adjusted life year gained.The incremental cost-effectiveness ratio of pemetrexed and docetaxel compared with gemcitabine exceeded the willingness-to-pay threshold.One-way sensitivity analysis showed that the utility value of gemcitabine in the progressed survival state was the most influential parameter.
基金Beijing Natural Science Foundation(Grant No.7131009)the National Basic Research Program of China(Grant No.973 program,2013CB932501)+1 种基金the National Natural Science Foundation of China(Grant No.81373343)the Innovation Team of Ministry of Education(Grant No.BMU20110263)
文摘Multidrug resistance （MDR） of breast cancer is a major cause of failure in chemotherapy. In the present study, a distearoylphosphatidyl ethanolamine-polyethylene glycol-pemetrexed （DSPE-PEG2000-PMT） conjugate was synthesized from DSPE-PEG2000-NH2 and pemetrexed, and targeted sunitinib plus vinorelbine liposomes were developed by modifying DSPE-PEG20o0-PMT onto the surface of liposomes to overcome the MDR of breast cancer. The synthesized DSPE-PEG2000-PMT was confirmed to be consistent with the target product by matrix-assisted laser desorption/ionization time of flight mass spectrometry （MALDI-TOF-MS）. The concentrations of sunitinib and vinorelbine were measured simultaneously by high performance liquid chromatography （HPLC）. The analysis was performed on an ODS column at 30℃ at a wavelength of 215 nm with the mobile phase consisting of acetonitrile, 0.05 M KH2PO4 （pH 3.5） and triethylamine （35：65：0.3, v/v/v）. The limits of detection for sunitinib and vinorelbine were 25 ng/mL and 5 ng/mL, respectively, and the limits of quantification for both drugs were 0.25μg/mL. Two drugs were linearly correlated in the range of 0.5-25.0 μg/mL. For varying types of liposomes, the encapsulation efficiencies were 〉90%; the particle sizes were approximately 90 nm, and zeta potentials were slightly negative. The inhibitory effects were evaluated in the resistant breast cancer MCF-7/Adr cells. The results revealed that targeted sunitinib plus vinorelbine liposomes exhibited the strongest inhibitory effect to the resistant MCF-7/Adr cells among the varying formulations. Targeted coumarin liposomes were used as a fluorescent probe to evaluate the targeting effect to resistant breast cancer MCF-7/Adr cells. The results demonstrated that the targeted coumarin liposomes displayed the highest cellular uptake compared to non-targeted formulations. In conclusion, the targeted sunitinib plus vinorelbine liposomes represented a novel type of nano-formulations, which could accumulate in the resistant breast cancer cells, thereby inhibiting proliferation of the resistant cancer cells. Accordingly, the targeted sunitinib plus vinorelbine liposomes may provide a new strategy for circumventing the drug resistance in the resistant breast cancer.
