***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: BACKGROUND Recent dose-intensity studies of small-cell lung cancer ( SCLC ) have yielded conflicting results . We carried out a phase III r and omized trial in patients with better-prognosis SCLC ( i.e. , prognostic score of 0 - 1 ) to investigate whether doubling the dose density of ifosfamide , carboplatin , and etoposide ( ICE ) chemotherapy with filgrastim and blood-progenitor-cell support improves survival , compared with st and ard ICE chemotherapy . METHODS We studied 318 patients with pathologically proven SCLC who were r and omly assigned to receive six cycles of ICE chemotherapy with a 4-week ( st and ard arm ) or 2-week ( dose-dense arm ) interval between cycles . Patients in the dose-dense arm received filgrastim subcutaneously daily on days 4 through 14 and had autologous blood collected before cycles 2 through 6 , which was returned 24 hours after treatment . Toxicities , including hematologic toxicity and incidence of neutropenic sepsis , were monitored . Survival was calculated by the Kaplan-Meier method . All statistical tests were two-sided . RESULTS The delivered median dose intensity was 99 % ( interquartile range = 96%-100 % ) for the st and ard arm and 182 % ( interquartile range = 163%-196 % ) for the dose-dense arm . After a median follow-up of 14 months , overall response to treatment was observed in 118 ( 80 % ) of the 148 evaluable patients in the st and ard arm and in 129 ( 88 % ) of the 147 evaluable patients in the dose-dense arm , a statistically non-significant difference . Median overall survival was 13.9 months ( 95 % confidence interval [ CI ] = 12.9 to 15.8 months ) in the st and ard arm and 14.4 months ( 95 % CI = 12.7 to 16.0 ) in the dose-dense arm , and the 2-year survival was 22 % ( 95 % CI = 16 % to 29 % ) and 19 % ( 95 % CI = 14 % to 27 % ) , respectively -- neither difference being statistically significant . The median treatment free time was 286 days ( 95 % CI = 229 to 343 days ) for the st and ard arm and 367 days ( 95 % CI = 321 to 413 days ) for the dose-dense arm ( difference = 81 days ; P = .109 ) . Statistically significantly more hematologic toxicity was reported in the dose-dense arm than in the st and ard arm , but the number of cycles complicated by neutropenic sepsis was statistically significantly higher in the st and ard arm than in the dose-dense arm ( 15.3 % versus 11.6 % , respectively ; difference = 3.7 % , 95 % CI = -4.1 % to 11.5 % ; P = .03 ) . CONCLUSIONS Dose-dense ICE chemotherapy for SCLC led to shorter treatment duration and less neutropenic sepsis than did st and ard ICE but did not improve 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 PURPOSE The purpose of this study was to assess the activity and toxicity of a combined regimen of topotecan and cisplatin in " sensitive " ( s ) and " refractory " ( r ) small-cell lung cancer ( SCLC ) patients treated previously . EXPERIMENTAL DESIGN Patients with measurable SCLC and progressive disease after one first-line regimen were eligible for the study . Patients were enrolled in two separate groups : r group ( patients who failed first-line treatment <3 months from treatment discontinuation ) and s group ( patients who responded to first-line treatment and progressed > or=3 months after treatment discontinuation ) . Cisplatin was given i.v . at the dose of 60 mg/m(2 ) on day 1 , and topotecan was administered as a daily i.v . infusion at the dose of 0.75 mg/m(2 ) from day 1 to 5 , every 3 weeks . RESULTS A total of 110 eligible ( 68 s and 42 r ) patients were enrolled from 24 institutions . The main patient characteristics were as follows : median age 60 ( s ) and 55 ( r ) years , median performance status 1 for both ( s ) and ( r ) . Seventy-four percent ( s ) and 67 % ( r ) had extensive stage disease , including 22 % and 36 % , respectively , with brain metastases . A total of 398 chemotherapy courses were administered [ median 4 ( s ) and 3 ( r ) per patient ] . The most frequent and serious toxicity was myelosuppression . Grade IV neutropenia occurred in 62 % ( s ) and 49 % ( r ) of patients , with a 19 % ( s ) and 15 % ( r ) incidence of febrile neutropenia , and grade IV thrombocytopenia in 54 % ( s ) and 44 % ( r ) . Most of these toxicities occurred during the first chemotherapy course and led to topotecan dose reduction and /or delay in the following courses . Grade III-IV nonhematological toxicity was uncommon . Five deaths possibly related to toxicity occurred among s patients only . Objective responses have been documented in 20 s patients , 19 partial responses and 1 complete response , ( 29.4 % response rate ; 95 % confidence interval , 19 - 42 ) , whereas , among r patients , 10 partial responses have been observed ( 23.8 % response rate ; 95 % confidence interval , 12 - 39 ) . Median survival for s and r was 6.4 and 6.1 months , respectively . CONCLUSIONS The combination of cisplatin and topotecan , at this dose and schedule , shows activity and promising results in patients with refractory SCLC , with reversible myelosuppression being the main side effect . Additional development of this regimen , using better-tolerated schedules , is warranted in patients with refractory SCLC BACKGROUND Previous phase I-II studies have shown that the combination of paclitaxel-cisplatin-etoposide ( TEP ) is very active and well tolerated in patients with small-cell lung cancer ( SCLC ) . In order to compare the TEP combination to cisplatin etoposide ( EP ) regimen as front-line treatment in patients with SCLC , we conducted a r and omised multicenter study . PATIENTS AND METHODS One hundred thirty-three chemotherapy-naïve patients with histologically proven limited or extensive stage SCLC were r and omised to receive either paclitaxel 175 mg/m2 i.v . three-hour infusion on day 1 and cisplatin 80 mg/m2 i.v . on day 2 and etoposide 80 mg/m2 i.v . on days 2 - 4 with G-CSF support ( 5 mcg/kg s.c . days 5 - 15 ) or cisplatin 80 mg/m2 i.v . on day 1 and etoposide 120 mg/m2 i.v . on days 1 - 3 in cycles every twenty-eight days . RESULTS Due to excessive toxicity and mortality observed in the TEP arm , an early interim analysis was performed and the study was closed . Sixty-two patients received two hundred sixty-one cycles of TEP and seventy-one patients three hundred twenty-three cycles of EP The two patient groups were well balanced for age , sex , performance status , stage of disease and the presence of abnormal LDH at diagnosis . In an intention-to-treat overall analysis both regimens were equally active with a complete and partial response rate of 50 % ( 95 % confidence interval ( CI ) : 37.5%-62.4 % ) for TEP and 48 % ( 95 % ) CI : 36.2%-59.5 % ) for EP ( P = 0.8 ) . The median time to disease progression was 11 months for TEP and 9 months for EP ( P = 0.02 ) . The duration of response , one-year survival and overall survival were similar in the two arms . Similarly , in an intention-to-treat subgroup analysis of patients with limited or extensive stage disease , there was no difference in the activity between the two regimens except of a longer median time to disease progression in the extensive stage in favour of the TEP regimen , eight versus six months ( P = 0.04 ) . However , there were eight toxic deaths in the TEP arm versus none in the EP arm ( P = 0.001 ) . Moreover , the TEP regimen was associated with more severe toxicity than the EP regimen in terms of grade 4 neutropenia ( P = 0.04 ) , grade 3 - 4 thrombocytopenia ( P = 0.02 ) , febrile neutropenia ( P = 0.08 ) , grade 3 - 4 diarrhea ( P = 0.01 ) , grade 3 - 4 asthenia ( P = 0.05 ) and grade 3 neurotoxicity ( P = 0.06 ) . CONCLUSIONS In this early terminated study , the TEP regimen was significantly more toxic than the EP regimen . The TEP regimen is associated with significant toxicity and mortality , and should not be used outside of a protocol setting . For future investigations , dose and schedule modifications are necessary to reduce toxicity BACKGROUND This phase II study evaluated the efficacy and safety of the irinotecan/gemcitabine combination in patients with relapsed/refractory small-cell lung cancer ( SCLC ) . PATIENTS AND METHODS Patients with measurable tumor who had received one previous chemotherapy or chemotherapy/radiation regimen were eligible .  Gemcitabine 1000 mg/m(2 ) was administered i.v . over 30 min followed immediately by irinotecan 100 mg/m(2 ) i.v . over 90 min , both on days 1 and 8 every 21 days . Patients were stratified based on response to initial treatment [ i.e. primary sensitive disease with progression > or=3 months ( group A ) , or refractory disease ( group B ) ] . RESULTS Seventy-three patients were enrolled but one never received treatment and one ineligible patient did not have SCLC . Median patient ages of the remaining patients were 61 and 63 years in groups A ( n = 35 ) and B ( n = 36 ) , respectively , with performance status of 0 or 1 in 85 % of 71 patients . Primary grade 3/4 toxic effects in groups A versus B were neutropenia ( 36 % versus 43 % ) , thrombocytopenia ( 36 % versus 26 % ) , nausea ( 12 % versus 11 % ) , vomiting ( 0 versus 11 % ) , diarrhea ( 12 % versus 9 % ) , and pulmonary ( 12 % versus 12 % ) . Two patients had fatal events including pneumonitis ( n = 1 ) and acute respiratory distress syndrome ( n = 1 ) . Responses occurred in 11 group A [ two complete responses and nine partial responses ( PRs ) ] and four group B ( all PRs ) patients , for response rates of 31 % [ 95 % confidence interval ( CI ) 17 % , 49 % ) and 11 % ( 95 % CI 3 % , 26 % ) , respectively . Median survival and progression-free survival times were 7.1 ( 95 % CI 6 , 10.5 ) versus 3.5 ( 95 % CI 3.1 , 5.7 ) months , and 3.1 ( 95 % CI 1.6 , 5.3 ) versus 1.6 ( 95 % CI 1.4 , 2.8 ) months for group A versus B. CONCLUSION The irinotecan/gemcitabine combination is active and well tolerated as second-line therapy in SCLC patients . Additional studies are warranted as second-line therapy in patients who progressed 90 days or more after first-line therapy . However , the observed efficacy results 
    Output:
    
The meta- analysis of topotecan regimens ( TP ) was not reliable due to impending heterogeneity .
The present meta- analysis demonstrates statistically significant OS and PFS benefits of IP over EP regimens in western and eastern patients .