metastatic or loco - regionally advanced non - small cell lung carcinoma ( nsclc ) is one of the leading causes of death attacked with cancer in india and though treatment outcomes in advanced disease remain modest , with the paradigm shift in the approach to treatments customized treatment based on the tumor histology and genetic profiles have become the standard of care . systemic chemotherapy with the platinum based doublets is the standard of care in metastatic or advanced nsclc . however , patients with advanced or metastatic disease eventually present disease progression and needs second - line systemic therapy in a selected group of patients or other supportive measures . second - line chemotherapy with docetaxel had shown to improve overall survival ( os ) by means of 3 months and to delay the deterioration of quality - of - life in patients with good performance status . pemetrexed is another anti - folate approved for use in non - squamous histology nsclc as second - line chemotherapy and has emerged as a preferred option in this sub - group . the ncic trial br21 had shown that the benefit of erlotinib after of first - line chemotherapy in nsclc . treatment with erlotinib improves progression free survival ( pfs ) ( hazard ratio : 0.61 , p=0.001 ) and then erlotinib approved for the treatment of advanced nsclc after the failure of upfront chemotherapy . interest , phase iii high - powered randomized study and the patients randomized to receive gefitinib or docetaxel as second - line therapy . the analysis showed that the objective response and survival were similar in the two groups and consequently approved as second - line therapy in nsclc . in spite of the clinical benefit of the second - line treatment , there are reliable predictors of objective response , those who received first - line chemotherapy , but very little knowledge available from literature about the prognostic variables in patients , who receive second - line therapy . there is a modest survival advantage in second - line therapy , at the same time leaves toxic side - effect . we need to find out robust clinical and demographic predictive and prognostic factors to guide the second - line therapy in nsclc after disease progression . the objective of this study was to identify the clinical or demographic predictive factors for survival of advanced or metastatic nsclc who received second - line therapy . we retrospectively reviewed 329 patients received second - line treatment from july 2007 to september 2011 in the department of radiation oncology , burdwan medical college and hospital . they met the following inclusion criteria ; 
 histological or cytological proof of nsclcstage iii - iv ( brain metastasis excluded)received first - line platinum based doublet chemotherapythey had measurable disease as defined by who criteriathey were 18 years or older in age . 
  histological or cytological proof of nsclc stage iii - iv ( brain metastasis excluded ) received first - line platinum based doublet chemotherapy they had measurable disease as defined by who criteria they were 18 years or older in age . a total of 12 potential prognostic variables were chosen as the basis of previously published clinical trials . the variables were categorized as 
 age ( 60 years vs. > 60 years)sex ( male / female)performance status ( ecog 0 - 1/2 - 3)smoking status ( never smoker / smoker or formerly smoker)serum lactate dehydrogenase ( normal / elevated)histology ( adenocarcinoma / non - adenocarcinoma)stage at diagnosis ( stage iiia and iiib or stage iv)first - line chemotherapy ( platinum based doublet , etoposide vs. paclitaxel or gemcitabine or pemetrexed)response to first - line chemotherapy ( clinical disease control or progressive disease)pfs after first - line chemotherapy ( 6 months/>6 months)site of failure ( intrathoracic vs. intra - thoracic and distant / distant / brain metastasis)second - line chemotherapy ( base supportive care vs. docetaxel / pemetrexed / erlotinib / gefitinib ) 
  age ( 60 years vs. > 60 years ) performance status ( ecog 0 - 1/2 - 3 ) smoking status ( never smoker / smoker or formerly smoker ) serum lactate dehydrogenase ( normal / elevated ) histology ( adenocarcinoma / non - adenocarcinoma ) stage at diagnosis ( stage iiia and iiib or stage iv ) first - line chemotherapy ( platinum based doublet , etoposide vs. paclitaxel or gemcitabine or pemetrexed ) response to first - line chemotherapy ( clinical disease control or progressive disease ) pfs after first - line chemotherapy ( 6 months/>6 months ) site of failure ( intrathoracic vs. intra - thoracic and distant / distant / brain metastasis ) second - line chemotherapy ( base supportive care vs. docetaxel / pemetrexed / erlotinib / gefitinib ) all of the analysis performed using the spss statistical software program package ( spss version 16 , spss inc . , chicago ) . the difference of the clinical characteristic between the groups was analyzed by chi - square test and student t - test . os calculated from the first cycle of chemotherapy to the date of death from any cause or the date of last follow - up . survival after second - line chemotherapy calculated from the 1 day of starting second - line therapy to the date of death from any cause or date of last follow - up . pfs defined as the period from the first day of chemotherapy until the progression of disease or death . we retrospectively reviewed 329 patients received second - line treatment from july 2007 to september 2011 in the department of radiation oncology , burdwan medical college and hospital . they met the following inclusion criteria ; 
 histological or cytological proof of nsclcstage iii - iv ( brain metastasis excluded)received first - line platinum based doublet chemotherapythey had measurable disease as defined by who criteriathey were 18 years or older in age . 
  histological or cytological proof of nsclc stage iii - iv ( brain metastasis excluded ) received first - line platinum based doublet chemotherapy they had measurable disease as defined by who criteria they were 18 years or older in age . a total of 12 potential prognostic variables were chosen as the basis of previously published clinical trials . the variables were categorized as 
 age ( 60 years vs. > 60 years)sex ( male / female)performance status ( ecog 0 - 1/2 - 3)smoking status ( never smoker / smoker or formerly smoker)serum lactate dehydrogenase ( normal / elevated)histology ( adenocarcinoma / non - adenocarcinoma)stage at diagnosis ( stage iiia and iiib or stage iv)first - line chemotherapy ( platinum based doublet , etoposide vs. paclitaxel or gemcitabine or pemetrexed)response to first - line chemotherapy ( clinical disease control or progressive disease)pfs after first - line chemotherapy ( 6 months/>6 months)site of failure ( intrathoracic vs. intra - thoracic and distant / distant / brain metastasis)second - line chemotherapy ( base supportive care vs. docetaxel / pemetrexed / erlotinib / gefitinib ) 
  age ( 60 years vs. > 60 years ) performance status ( ecog 0 - 1/2 - 3 ) smoking status ( never smoker / smoker or formerly smoker ) serum lactate dehydrogenase ( normal / elevated ) histology ( adenocarcinoma / non - adenocarcinoma ) stage at diagnosis ( stage iiia and iiib or stage iv ) first - line chemotherapy ( platinum based doublet , etoposide vs. paclitaxel or gemcitabine or pemetrexed ) response to first - line chemotherapy ( clinical disease control or progressive disease ) pfs after first - line chemotherapy ( 6 months/>6 months ) site of failure ( intrathoracic vs. intra - thoracic and distant / distant / brain metastasis ) second - line chemotherapy ( base supportive care vs. docetaxel / pemetrexed / erlotinib / gefitinib ) all of the analysis performed using the spss statistical software program package ( spss version 16 , spss inc . , chicago ) . the difference of the clinical characteristic between the groups was analyzed by chi - square test and student t - test . os calculated from the first cycle of chemotherapy to the date of death from any cause or the date of last follow - up . survival after second - line chemotherapy calculated from the 1 day of starting second - line therapy to the date of death from any cause or date of last follow - up . pfs defined as the period from the first day of chemotherapy until the progression of disease or death . between july 2007 and september 2011 , 329 patients received second - line systemic therapy or best supportive care ( bsc ) after failing platinum based doublet chemotherapy . patients with good ( ecog 0 - 1 ) and poor performance ( ecog 2 - 3 ) status was 66.3% and 33.7% respectively . the median survival after the starting of second - line treatment or bsc was 5 months . baseline characteristic of patients the results of univariate analysis of survival after second - line treatment and os are summarized in table 2 . among the 12 variables included for binary logistic analysis , all the above identified to have significant prognostic factors for survival after second - line treatment except the stage at diagnosis , 1 line chemotherapy and site of failure after 1 line chemotherapy . univariate analysis of categorical variables multivariate analysis by cox regression model included the prognostic significant variables from the univariate analysis . multivariate analysis by cox regression model has shown that performance status ( ps ) and second - line treatments were independent prognostic factors for survival after second - line treatment . furthermore , performance status , age , smoking habits , pfs after 1 line therapy and second - line therapy were the variables considered an independent prognostic factor for os [ tables 3 and 4 , figures 14 ] . multivariate analysis of categorical variables by cox regression model for survival after second line therapy and os prognostic variables , os and survival after second - line treatment kaplan - meier curve estimates of overall survival in patients with ecog 0 - 1 or ecog 2 - 3 performance status kaplan - meier curve estimates of survival after second - line therapy in patients with ecog 0 - 1 or ecog 2 - 3 performance status kaplan - meier curve estimates of overall survival in patients treated with docetaxel / pemetrexed / erlotinib / gefitinib or best supportive care kaplan - meier curve estimates of survival after second line therapy in patients treated with docetaxel / pemetrexed / erlotinib / gefitinib or best supportive care between july 2007 and september 2011 , 329 patients received second - line systemic therapy or best supportive care ( bsc ) after failing platinum based doublet chemotherapy . patients with good ( ecog 0 - 1 ) and poor performance ( ecog 2 - 3 ) status was 66.3% and 33.7% respectively . the median survival after the starting of second - line treatment or bsc was 5 months . the results of univariate analysis of survival after second - line treatment and os are summarized in table 2 . among the 12 variables included for binary logistic analysis , all the above identified to have significant prognostic factors for survival after second - line treatment except the stage at diagnosis , 1 line chemotherapy and site of failure after 1 line chemotherapy . univariate analysis of categorical variables multivariate analysis by cox regression model included the prognostic significant variables from the univariate analysis . multivariate analysis by cox regression model has shown that performance status ( ps ) and second - line treatments were independent prognostic factors for survival after second - line treatment . furthermore , performance status , age , smoking habits , pfs after 1 line therapy and second - line therapy were the variables considered an independent prognostic factor for os [ tables 3 and 4 , figures 14 ] . multivariate analysis of categorical variables by cox regression model for survival after second line therapy and os prognostic variables , os and survival after second - line treatment kaplan - meier curve estimates of overall survival in patients with ecog 0 - 1 or ecog 2 - 3 performance status kaplan - meier curve estimates of survival after second - line therapy in patients with ecog 0 - 1 or ecog 2 - 3 performance status kaplan - meier curve estimates of overall survival in patients treated with docetaxel / pemetrexed / erlotinib / gefitinib or best supportive care kaplan - meier curve estimates of survival after second line therapy in patients treated with docetaxel / pemetrexed / erlotinib / gefitinib or best supportive care docetaxel , pemetrexed and tkis ( erlotinib and gefitinib ) have significantly changed the treatment paradigm for advanced nsclc . however , the optimal integration of first - line and second - line chemotherapy is yet to be defined . at this time , the selection of second - line cytotoxic agent or only the bsc may depends numbers of factors including physician preferences , patients preferences , smoking history , smoking history and tumor histology . give the incurable nature of the advanced nsclc and modest survival seen after second - line setting , patient 's preferences and convenience should considered when selecting the second - line agents . few prior studies had shown that performance status , gender , histopathology , stage at diagnosis , type of initial chemotherapy , the best response to first - line chemotherapy , pfs after upfront chemotherapy have strong predictive value in os and os after second - line chemotherapy in univariate analysis . however , this trend did not persist in multivariate regression analysis ; the only variables have a strong correlation where the ps of patients and response to first - line chemotherapy . this retrospective study has shown the potential influence of ps and the second - line cytotoxic therapy on the outcome of the second - line treatments and the ps as well as age , smoking habits , pfs and second - line therapy had strong predictive value in os . the outcomes were similar regardless of the response to first - line cyto - toxic therapy and did not accord with the results of . this might be due in inadequate treatment with first - line chemotherapy containing etoposide and retrospective review analysis . the importance of ps also confirmed in our study and has shown poor ps had a negative effect on os and survival after second - line therapy or bsc only . the current study demonstrated that the poor ps not only had a negative effect on os , also did not tolerate second - line cytotoxic treatment due to toxicity . it remains ambiguous whether stage at the time of diagnosis ( iiia , iiib or iv ) in patients receiving second - line cytotoxic agent will ensure prognostic knowledge for os . , di maio et al . , scartozzi et al . had shown significant predictive value of stage at diagnosis on the os while di maio et al . and zietemann and duell did not mention the prognostic value of the stage . in our study , stage at diagnosis did not identify as a prognostic variable for os or survival after second - line treatment . this may be due to retrospective analysis , the difference of the treatment choice and etoposide included in the first - line chemotherapy regimen . the main limitation of this study was retrospective study , we did not evaluate the molecular characteristic of tumor and first - line chemotherapy did not base upon the histopathology and small number of patients included for analysis . the ps has shown consistent result as a prognostic factor in univariate and multivariate analysis for os and survival after second - line systemic treatment . these findings may also facilitate pretreatment prediction of survival and be used for selecting patients for the correct choice of cyto - toxic therapy . more prospective multicentric randomized studies are required to answer the treatment option in the second - line therapy in nsclc or beyond . two additional areas that may be worth pursuing in the data collection would be quality - of - life improvement and toxicity experiences by the patients during or after second - line therapy .