Q Kong1, X Y Wang1, R C Jiang1, Y Ba2, K Li1. 1. Department of Thoracic Oncology, the National Center for Clinical Medicine Research, Tianjin Lung Cancer Center, Tianjin Cancer Institute & Hospital, Tianjin Medical University, Tianjin 300060, China. 2. Digestion Oncology, the National Center for Clinical Medicine Research, Tianjin Lung Cancer Center, Tianjin Cancer Institute & Hospital, Tianjin Medical University, Tianjin 300060, China.
Abstract
OBJECTIVE: The purpose of this study is to explore the efficacy and predictors of second-line chemotherpy in advanced non-small cell lung cancer patients and suggest optimal protocols suitable for differently characterized patients. METHODS: The clinical data of 178 advanced NSCLC patients second-line-treated in Tianjin Cancer Hospital from 2009.1.1 to 2013.12.31 were retrospectively analyzed. According to the different second-line treatments, the patients were divided into standard mono-drug therapy group (46 cases), endostar combined with standard mono-drug therapy group (42 cases), and platinum-based doublet chemotherapy group (90 cases). Kaplan-Meier and Log-rank analyses were used to estimate and compare the survival rates in the groups, and Cox's hazard regression model was used to determine the prognostic factors. Chi-square test was used to analyze the differences among different groups. RESULTS: The median progression-free survivals (mPFS) were 50 days, 54 days, and 79 days (P=0.042) for the standard mono-drug therapy group, endostar combined with standard mono-drug therapy group, and platinum-based doublet chemotherapy group, respectively. The differences between the mono-drug therapy group and doublet chemotherapy group were statistically significant (P=0.011). The disease control rate (DCR) for each group was 26.1%, 47.6% and 46.7% (P=0.041), and the DCR were statistically significantly different between the mono-drug therapy group and doublet chemotherapy group (P=0.016), and between the mono-drug therapy group and endostar combined with standard mono-drug therapy group (P=0.041). The overall response rate (ORR) for each group was 2.2%, 0, and 4.4% (P>0.05 for all). Multivariate analysis showed that the period from the begining of first-line to second-line chemotherapy (progression-free time), base-line clinical stage, neuron specific enolase (NSE) before second-line therapy, the cycles of second-line chemotherapy and the response to second-line therapy were independent predictors for PFS (P<0.005 for all). Subgroup analysis indicated that the patients obtained more clinical benefit from doublet chemotherapy rather than mono-drug therapy, with following factors: age<60 years, paclitaxel plus cisplatin for first-line treatment, chemotherapy cycles ≤4, CR, PR and SD for response, progression time within 3-6 months from the begining of first-line to second-line chemotherapy, performance status score≤1 at the begining of second-line therapy, Ⅳ stage, and mild leukopenia (P<0.05 for all). The patients whose progression-free survival time within 3-6 months from the begining of the first-line to second-line chemotherapy got more clinical benefit from endostar combined with standard mono-drug chemotherapy than mono-drug therapy (P=0.006). CONCLUSIONS: The period from the begining of first-line to second-line chemotherapy, base-line TNM stage, NSE before second-line chemotherapy, the cycles of second-line chemotherapy and the response to second-line therapy were independent predictors for PFS. Platinum-based doublet chemotherapy and endostar plus standard second-line regimen can improve the efficacy in some characterized advanced NSCLC as compared with the patients by standard mono-drug therapy, wherein the platinum-based chemotherapy revealed the best efficacy.
OBJECTIVE: The purpose of this study is to explore the efficacy and predictors of second-line chemotherpy in advanced non-small cell lung cancerpatients and suggest optimal protocols suitable for differently characterized patients. METHODS: The clinical data of 178 advanced NSCLCpatients second-line-treated in Tianjin Cancer Hospital from 2009.1.1 to 2013.12.31 were retrospectively analyzed. According to the different second-line treatments, the patients were divided into standard mono-drug therapy group (46 cases), endostar combined with standard mono-drug therapy group (42 cases), and platinum-based doublet chemotherapy group (90 cases). Kaplan-Meier and Log-rank analyses were used to estimate and compare the survival rates in the groups, and Cox's hazard regression model was used to determine the prognostic factors. Chi-square test was used to analyze the differences among different groups. RESULTS: The median progression-free survivals (mPFS) were 50 days, 54 days, and 79 days (P=0.042) for the standard mono-drug therapy group, endostar combined with standard mono-drug therapy group, and platinum-based doublet chemotherapy group, respectively. The differences between the mono-drug therapy group and doublet chemotherapy group were statistically significant (P=0.011). The disease control rate (DCR) for each group was 26.1%, 47.6% and 46.7% (P=0.041), and the DCR were statistically significantly different between the mono-drug therapy group and doublet chemotherapy group (P=0.016), and between the mono-drug therapy group and endostar combined with standard mono-drug therapy group (P=0.041). The overall response rate (ORR) for each group was 2.2%, 0, and 4.4% (P>0.05 for all). Multivariate analysis showed that the period from the begining of first-line to second-line chemotherapy (progression-free time), base-line clinical stage, neuron specific enolase (NSE) before second-line therapy, the cycles of second-line chemotherapy and the response to second-line therapy were independent predictors for PFS (P<0.005 for all). Subgroup analysis indicated that the patients obtained more clinical benefit from doublet chemotherapy rather than mono-drug therapy, with following factors: age<60 years, paclitaxel plus cisplatin for first-line treatment, chemotherapy cycles ≤4, CR, PR and SD for response, progression time within 3-6 months from the begining of first-line to second-line chemotherapy, performance status score≤1 at the begining of second-line therapy, Ⅳ stage, and mild leukopenia (P<0.05 for all). The patients whose progression-free survival time within 3-6 months from the begining of the first-line to second-line chemotherapy got more clinical benefit from endostar combined with standard mono-drug chemotherapy than mono-drug therapy (P=0.006). CONCLUSIONS: The period from the begining of first-line to second-line chemotherapy, base-line TNM stage, NSE before second-line chemotherapy, the cycles of second-line chemotherapy and the response to second-line therapy were independent predictors for PFS. Platinum-based doublet chemotherapy and endostar plus standard second-line regimen can improve the efficacy in some characterized advanced NSCLC as compared with the patients by standard mono-drug therapy, wherein the platinum-based chemotherapy revealed the best efficacy.