***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: The prognosis of patients with locally advanced nonsmall cell lung carcinoma ( NSCLC ) , which is usually unresectable , is very poor , and patient survival rarely reaches 1 year . However , prolonged survival correlated with objective responses has been observed among patients with intrathoracic disease treated with a combination of cytotoxic drugs and local irradiation despite the lack of consensus regarding the schedule of such combined therapy . From October 1989 to November 1993 , a Phase II study was conducted to evaluate the tolerability and efficacy  of alternating chemotherapy and accelerated split‐course radiotherapy in the treatment of patients with locally advanced NSCLC Introduction : As a result of recent publications , we hypothesized that period of 8 weeks after initiation of treatment is a useful l and mark point for cytotoxic agents for advanced non-small cell lung cancer ( NSCLC ) . To test this hypothesis , we conducted l and mark analyses with clinical trials employing cytotoxic agents . Our goal was to assess the proper design of clinical trials with cytotoxic agents for NSCLC for maximizing patients ’ benefit . Methods : We conducted l and mark analyses of a phase II study of pemetrexed in locally advanced or metastatic NSCLC and a phase III study of Four-Arm Cooperative Study for advanced NSCLC . A total of 806 patients who received chemotherapy ( pemetrexed , cisplatin and irinotecan , paclitaxel and carboplatin , cisplatin and gemcitabine , cisplatin and vinorelbine )  were included in this assessment . Results : Tumor-shrinkage rate at 8 weeks was significantly associated with longer survival in the study with pemetrexed ( p = 0.043 ) , whereas tumor-shrinkage rate at 4 weeks did not correlated with survival ( p = 0.139 ) . Similarly , using the Four-Arm Cooperative Study data , the optimal l and mark point was 8 weeks ( p = 0.002 ) , not 4 weeks ( p = 0.190 ) . Conclusion : The l and mark point for NSCLC was 8 weeks with all cytotoxic agents in our analysis when the therapy was given as a frontline or subsequent therapy . Our result suggests the concept of a disease-specific l and mark point , which may lead to a change of phase II/III clinical study design to evaluate cytotoxic agents and clinical investigators , and their sponsors may consider an early look to assess the efficacy of cytotoxic agents for NSCLC BACKGROUND We conducted a r and omized , placebo-controlled , double-blind trial to determine whether the epidermal growth factor receptor inhibitor erlotinib prolongs survival in non-small-cell lung cancer after the failure of first-line or second-line chemotherapy . METHODS Patients with stage IIIB or IV non-small-cell lung cancer , with performance status from 0 to 3 , were eligible if they had received one or two prior chemotherapy regimens .  The patients were stratified according to center , performance status , response to prior chemotherapy , number of prior regimens , and prior platinum-based therapy and were r and omly assigned in a 2:1 ratio to receive oral erlotinib , at a dose of 150 mg daily , or placebo . RESULTS The median age of the 731 patients who underwent r and omization was 61.4 years ; 49 percent had received two prior chemotherapy regimens , and 93 percent had received platinum-based chemotherapy .  The response rate was 8.9 percent in the erlotinib group and less than 1 percent in the placebo group ( P<0.001 ) ; the median duration of the response was 7.9 months and 3.7 months , respectively . Progression-free survival was 2.2 months and 1.8 months , respectively ( hazard ratio , 0.61 , adjusted for stratification categories ; P<0.001 ) . Overall survival was 6.7 months and 4.7 months , respectively ( hazard ratio , 0.70 ; P<0.001 ) , in favor of erlotinib . Five percent of patients discontinued erlotinib because of toxic effects . CONCLUSIONS Erlotinib can prolong survival in patients with non-small-cell lung cancer after first-line or second-line chemotherapy PURPOSE To determine the radiosensitizing effect of prolonged exposure of carboplatin in patients with locally unresectable non-small-cell lung cancer ( NSCLC ) . PATIENTS AND METHODS Patients with histologically proven NSCLC , performance score < 2 , weight loss < 10 % , and normal organ functions were r and omized between carboplatin 840 mg/m2 administered continuously during 6 weeks of radiotherapy or thoracic radiotherapy alone ( both 60 Gy ) . Toxicity was evaluated with National Cancer Institute Common Toxicity Criteria ( NCI CTC ) and the Radiation Therapy Oncology Group ( RTOG ) criteria . Quality of life was measured with European Organization for Research and Treatment of Cancer ( EORTC ) QLQ-C30/LC13 question naires . RESULTS One-hundred and sixty patients were included . Pathologically confirmed persistent tumor was present in 53 % of patients in the combination arm versus 58 % in the radiotherapy alone arm ( P=0.5 ) . Median survival in the combination arm was 11.8 [ 95 % confidence interval ( CI ) 9.3 - 14.2 ] months and in the radiotherapy alone arm 11.7 ( 95 % CI 8.1 - 15.5 ) months ; progression-free survival was not different between arms [ 6.8 and 7.5 months , respectively ( P=0.28 ) ] . Acute toxicity was mild , late toxicity was radiation-induced cardiomyopathy ( three patients ) and pulmonary fibrosis ( five patients ) . Quality of life was not different between arms , but in all measured patients cough and dyspnea improved , pain became less , and slight paresthesia developed 3 months after treatment . CONCLUSION Addition of continuously administered carboplatin as radiosensitizer for locally unresectable NSCLC does not improve local tumor control or overall survival BACKGROUND The duration of , re sources required for and cost of clinical trials could be reduced if a surrogate end point was to be used in place of survival . We assessed the extent to which the objective response rate ( ORR ) is predictive of mortality , how much difference in the ORR is needed to predict an obvious survival difference and what factors could affect the association between the two parameters during the first-line treatment of extensive disease (ED)-small-cell lung cancer ( SCLC ) . METHODS We used the  ORRs and median survival times ( MSTs ) from 48 phase III trials of first-line chemotherapy involving 8779 r and omised patients with ED-SCLC in a linear regression analysis . The MST difference was calculated as the difference in MST between the investigational and reference arms ; the ORR difference was similarly defined . RESULTS ORR difference between the treatment arms was modestly associated with the MST difference in the overall trials ( R(2 ) = 0.3314 ) . In contrast , the relationship was stronger among only trials in which prophylactic cranial irradiation was given to those having an objective response to the initial chemotherapy ( R(2 ) = 0.6279 ) . In this trial setting , large differences in ORR were needed to predict a survival advantage ( 1.2-day survival advantage per 2 % increase in ORR ) . CONCLUSIONS In the first-line treatment of ED-SCLC , a favourable relationship was detected between the two parameters in the selected trial setting . Large ORR differences were needed to predict a survival benefit , clearly suggesting the need for new chemotherapeutic agents To assess the clinical usefulness of serum pro-gastrin-releasing peptide ( Pro-GRP ) as a tumor marker for small cell lung carcinoma ( SCLC ) , we measured serum levels of Pro-GRP with a newly developed ELISA and measured serum levels of neuron-specific enolase ( NSE )  in 44 patients with untreated SCLC and 77 patients with untreated non-SCLC . We prospect ively measured serum levels of Pro-GRP and NSE in SCLC patients after initial treatment until relapse . The sensitivity ( 70 % ) and specificity ( 91 % ) of Pro-GRP were similar to those of NSE ( 70 and 86 % ) . Thirty-nine % of patients who had a partial response still had elevated serum levels of Pro-GRP at the time of restaging after initial treatment . In follow-up study , 94 % of patients had elevated serum levels of Pro-GRP again at the time of relapse , whereas 37 % of patients showed elevated levels of NSE . Levels of Pro-GRP increased a median of 35 ( -95 to 151 ) days before clinical evidence of relapse was detected with successive physical examinations and imaging studies , whereas levels of NSE increased 20 ( -85 to 124 ) days after relapse was detected ( P < 0.05 ) . Pro-GRP was helpful as a diagnostic aid and a marker for therapeutic effect and relapse in patients with SCLC , supplemented to serum NSE BACKGROUND The aim of this study was to analyse the outcome of surgically staged IIIA-N2 non-small-cell lung cancer ( NSCLC ) treated with induction chemotherapy followed by surgical exploration .  METHODS Univariate and multivariate analyses were carried out on a prospect i ve cohort of 131 mediastinoscopy-proven IIIA-N2 NSCLC patients . Three preoperative cycles of vindesine-ifosfamide-cisplatin ( VIP ) were given . Patients with at least stable disease ( SD ) were considered for surgery , or radical radiotherapy in selected cases . RESULTS The response rate after VIP was 54 % ( 95 % confidence interval 45 % to 63 % ) and was important for the final outcome . The median and 5-year survival for the total group were 24 months and 21 % ( 38 months and 30 % in responders ) , respectively . Involvement of subcarinal nodes at diagnosis was the most important prognostic factor ( P=0.022 ) . Seventy-five patients were considered for surgery .  Downstaging occurred in 34 of 70 resection specimens , with a pathological complete response in six . Median and 5-year survival in the surgical cohort were 45 months and 35 % , respectively . Surgery was rewarding both in patients with a response and in those with SD , although the complete resection rate was significantly lower in the latter . On multivariate analysis , favourable prognostic factors were low pathological T-stage ( P=0.001 ) and downstaging of mediastinal nodes in the resection specimen ( P=0.008 ) . CONCLUSIONS VIP induction chemotherapy followed by surgical exploration was rewarding in mediastinoscopy-proven stage IIIA-N2 NSCLC , both in cases of response and SD , despite a lower complete resection rate in the latter . Patients with subcarinal nodes at diagnosis ( 5-year survival 8.5 % ) or without nodal downstaging at post-induction surgery ( 13.7 % ) might preferably be treated with a non-surgical approach PURPOSE Patients with incurable cancer are faced with difficult decisions regarding whether to take chemotherapy in an attempt to preserve the quality and /or prolong the quantity of their lives . The average prolongation in survival with chemotherapy compared with best supportive care has not been well described . METHODS We performed a literature search using PUBMED combined with expert inquiry to identify trials comparing cytotoxic chemotherapy with best supportive care .  Twenty-five r and omized , controlled clinical trials comparing cytotoxic chemotherapy with best supportive care were identified . Sixteen trials ( 64 % ) were in patients with non-small-cell lung cancer ( NSCLC ) . Data were extracted and analyzed . RESULTS Sufficient data for statistical modeling were available for NSCLC trials . The mean sample size of the NSCLC trials was 175 patients .  Response rates in the treatment arms for NSCLC ranged from 7 % to 42 % . A relationship between response rate and survival was observed for NSCLC . The estimated relationship for NSCLC suggested that each 3.3 % increase in response rate correlated , on average , with a 1-week increase in median survival , and each 2 % increase in response rate correlated , on average , with a 1 % increase in 1-year survival . The mean increase in 1-year survival for trials of agents with at least a 20 % response rate in NSCLC was 16 % . Formulas are provided to help estimate how a given response rate may effect median and 1-year survival relative to best supportive care alone for NSCLC . CONCLUSION We found a relationship between response rate and both median and 1-year survival in NSCLC . This information may help oncologists estimate how an NSCLC chemotherapy regimen with a given response rate can , on average , impact survival relative to supportive care alone BACKGROUND Whether adjuvant chemotherapy improves survival of patients with non-small-cell lung cancer ( NSCLC ) is not known . We aim ed to compare the effect of adjuvant vinorelbine plus cisplatin versus observation on survival in patients with completely resected NSCLC . METHODS 840 patients with stage IB-IIIA NSCLC from 101 centres in 14 countries were r and omly assigned to observation ( n=433 ) or to 30 mg/m(2 ) vinorelbine plus 100 mg/m(2 ) cisplatin ( n=407 ) . Postoperative radiotherapy was not m and atory and was undertaken according to every centre 's policy . The primary endpoint was overall survival . Analysis was by intention to treat . This trial is registered as an International St and ard R and omised Controlled Trial , number IS RCT N9505 
    Output:
    
After review ing the literature with experts on these questions , it can be concluded that overall survival is still the best criterion for predicting treatment efficacy in lung cancer .