***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: We report the results of a r and omised trial in extensive small-cell lung cancer ( SCLC ) of a novel approach to palliative chemotherapy . A widely used 3 weekly regimen was compared with the same drugs given at half the dose but twice the frequency with the same intended overall dose intensity ( DI ) . A total of 167 patients defined as having extensive SCLC with adverse prognostic features were r and omised to receive either a 3 weekly regimen of cisplatin 60 mg m-2 i.v . on day 1 and etoposide 120 mg m-2 i.v . on day 1 and 100 mg b.d . orally on days 2 and 3 alternating with cyclophosphamide 600 mg m-2 i.v . , doxorubicin 50 mg m-2 i.v . and vincristine 2 mg i.v . all on day 1 for a maximum of six courses ( 3 weekly ) ; or treatment with the same drugs but with each course consisting of half the 3 weekly dose given every 10 or 11 days for a maximum of 12 courses . In the 10/11 day regimen overall response rate was 58.9 % ( 95 % CI , 47.9 - 69.2 % ) with 12.8 % complete responses ( CR ) . For the 3 weekly treatment the overall response rate was 44.9 % ( 95 % CI , 35.0 - 55.5 % ) with 10.1 % CR . Median survival was similar in the two arms at 6.4 months ( 95 % CI , 4.9 - 7.3 months ) and 5.8 months ( 95 % CI , 4.0 - 6.6 months ) respectively . Survival at 1 year was 9.9 % ( 95 % CI , 5.0 - 18.5 % ) and 8.9 % ( 95 % CI , 4.6 - 16.6 % ) . The 95 % CI for the difference in survival at 1 year is -7.09 % to + 9.09 % . Haematological toxicity and treatment delays owing to infection were more frequent with the 10/11 day regimen but other toxicities were equal in both arms . Other aspects of quality of life were measured in a small representative cohort of patients using a daily diary card ( DDC ) . There was a trend of improved quality of life on the 10/11 day arm , but there was little difference between the two treatments . The trial shows that a low-dose/high-frequency regimen with the same DI as conventionally scheduled chemotherapy gives similar response rates and survival . This and other modifications of the schedule may offer new approaches to palliative treatment of advanced cancer . However , in this trial there was no significant benefit in toxicity or other aspects of quality of life The question of whether initial prognostic factors in small-cell lung cancer patients have a predictive value for patients ' quality of life ( QL ) during chemotherapy is addressed in the context of a r and omised clinical trial comparing early and late alternating chemotherapy ( SAKK protocol 15/84 ) . The relative impact of initial tumour stage and performance status , previous weight loss , sex and age on patient-rated QL was analysed over six chemotherapy cycles in 124 - 130 patients ( according to available QL data ) with more than 400 question naires .  Fatigue/malaise , personal functioning , emotional and general well-being were prospect ively selected as QL indicators . Predefined summary measures ( average QL score over chemotherapy cycles , ' minimum ' , ' maximum ' and ' final ' improvement ) were analysed separately by scale in various patient groups . General linear models adjusted for treatment arm and response were used to confirm the univariate findings . Within the overall sample , the average QL scores over six cycles were predicted by initial prognostic factors . Patients with poor prognostic factors reported worse QL . Within a limited sample ( with baseline QL ) , patients with poor prognostic factors reported worse QL at baseline and greater improvement under treatment . Graphical comparison of QL patterns over cycles showed permanent discrimination by levels of prognostic factors . The impact of initial prognostic factors was consistently confirmed in the three analyses . Levels of performance status and weight loss best discriminated QL . Initial tumour stage , performance status and previous weight loss can predict QL in small-cell lung cancer during chemotherapy , even after controlling for response to treatment . Our results may contribute to clinical decision-making with regard to the intensity of chemotherapy and QL outcome , especially in patients with extensive disease Several studies of small cell lung cancer ( SCLC ) treatments have been performed in the United Kingdom . In some , prognostic factor analyses were carried out but the results were not entirely consistent . The Lung Cancer Subcommittee of the United Kingdom Coordinating Committee on Cancer Research ( UKCCCR ) consequently initiated an overview of these studies with the aim of identifying the important prognostic factors using a large number of patients . Information on almost 4,000 patients was available , but it was necessary to perform analyses on smaller subsets because the variables recorded in individual studies were inconsistent . A number of variables contributed significantly to the prediction of likely survival over the 6 months after starting treatment , but performance status ( PS ) , alkaline phosphatase ( AlkP ) and disease stage were shown to be the most important ; aspartate aminotransferase ( AST ) and lactate dehydrogenase ( LDH ) may also be useful . A prognostic index was devised for this initial period and vali date d using independent data . For patients who survived the first 6 months , the pre-treatment variables important for prognosis in the 6 - 24 month period were stage , PS and plasma sodium ( Na ) . The Subcommittee recommends that performance status , disease stage , AlkP , Na , AST and LDH should be measured in all future SCLC studies to assist comparisons between studies and possibly the selection of patients for different treatment strategies . The additional recording of five other variables would allow a more definitive overview to be performed at some future date BACKGROUND Patients with small-cell lung cancer ( SCLC ) that progress after first-line chemotherapy have a poor prognosis and the evidence of a benefit from second-line ( SL ) chemotherapy is limited . Patients relapsing or progressing more than 90 days after completion of first-line treatment are considered platinum sensitive and may be rechallenged with platinum-based chemotherapy . Topotecan is approved as SL treatment independent of time to progression . This retrospective analysis evaluates the clinical outcomes of SCLC patients who received SL chemotherapy after platinum-etoposide chemotherapy .  PATIENTS AND METHODS We retrospectively review ed 161 patients who received SL chemotherapy for SCLC . Patients were divided into four subgroups by type of SL treatment : ( 1 ) platinum-based rechallenge ; ( 2 ) anthracycline-based regimens ; ( 3 ) topotecan ; ( 4 ) other single agents . The endpoints were overall survival ( OS ) , progression-free survival ( PFS ) and response rate ( RR ) . Survival curves were plotted using the Kaplan-Meier method . The Cox proportional hazard model was used for multivariate analysis to investigate factors influencing survival . RESULTS The median age was 63 . There were 125 males and 36 females .  Eastern Cooperative Oncology Group performance status ( ECOG-PS ) was 0 , 1 and 2 in 12.5 % , 62.5 % and 25 % of patients , respectively . Platinum sensitive/platinum resistant/platinum refractory/unknown=121/29/3/8 patients . Median time to SL chemotherapy was 6.9 months . The median PFS from starting second-line treatment was 4.3 months and median OS was 5.8 months . The overall RR was 22.9 % . There was a trend toward higher RR ( 34.5 % vs 17.5 % , p for trend : 0.06 ) and OS ( 9.2 months vs 5.8 months , p=0.08 ) for patients with sensitive disease who were rechallenged with platinum-based chemotherapy . A multivariate analysis that adjusted for the time to SL treatment showed that a platinum-containing regimen achieves better RR , PFS and OS independently of the time to SL chemotherapy and that response to first-line treatment and PS at SL are the only independent prognostic factors . CONCLUSIONS The outcome for second-line therapy for SCLC was poor and benefit appeared to be limited to those patients with good PS and rechallenged with platinum-based chemotherapy . Platinum-based rechallenge should be considered as a st and ard comparator in future r and omized controlled trials of SL chemotherapy A total of 497 patients with histologically or cytologically confirmed small-cell lung cancer were prescribed initial treatment with six courses of etoposide , cyclophosphamide , methotrexate and vincristine at 3-week intervals . Patients with limited disease ( 74 % of the total ) also received radiotherapy ( 40 Gy in 15 fractions in 3 weeks ) to the primary site between courses 2 and 3 . At the end of this initial treatment , 265 patients still in complete or partial response were r and omly allocated to six further courses of maintenance chemotherapy ( M series : 131 patients ) or to no maintenance chemotherapy ( NoM series : 134 patients ) . Response , as assessed 3 weeks after the second course of initial chemotherapy , was achieved in 85 % of the 264 patients assessed , a complete response in 11 % . The median survival period from the date of start of chemotherapy was 39 weeks ; 154 ( 31 % ) of the patients were alive at 1 year , 29 ( 6 % ) at 2 years and 17 ( 3 % ) at 3 years . The patients ' general condition and extent of disease pretreatment correlated significantly with survival . Among the 131 M and 134 NoM patients there was no overall survival advantage to either series ( P = 0.27 , log rank test ) , although in 99 patients who had a complete response to initial chemotherapy as assessed at the time of r and omisation there was a suggestion that survival was longer in the M series ( P less than 0.05 , log rank test ) , the median survival periods from the date of r and omisation being 42 weeks for the M and 30 weeks for the NoM patients . Maintenance chemotherapy was associated with additional toxicity and a poorer quality of life as assessed intermittently by clinicians and daily by patients . In conclusion , no worthwhile clinical advantage was achieved by the policy of continuing chemotherapy beyond six courses , except possibly in patients with a complete response to the initial six courses Eighteen elderly patients aged 76 years or older with small cell lung cancer were treated with carboplatin ( AUC = 4 mg/ml.min , i.v . day 1 ) and etoposide ( 70 mg/m2 i.v . day 1 - 3 ) and 17 patients were evaluable . The median age of the study population was 77 years ( range : 76 - 81 ) . Eight patients had limited disease ( LD ) and nine did extensive disease ( ED ) . The overall response rate was 88 % for LD patients and 67 % for ED patients . Median survival time was 219 days for LD patients and 158 days for ED patients . Grade 3 and 4 leukopenia , neutropenia , thrombocytopenia and anemia occurred in 41 % , 76 % , 24 % and 6 % of patients , respectively . There was one treatment-related death due to pneumonitis PURPOSE To investigate whether chemotherapy with etoposide and cisplatin ( EP ) is superior to cyclophosphamide , epirubicin , and vincristine ( CEV ) in small-cell lung cancer ( SCLC ) . PATIENTS AND METHODS A total of 436 eligible patients were r and omized to chemotherapy with EP ( n = 218 ) or CEV ( n = 218 ) . Patients were stratified according to extent of disease ( limited disease [ LD ] , n = 214 ; extensive disease [ ED ] , n = 222 ) . The EP group received five courses of etoposide 100 mg/m(2 ) intravenously ( IV ) and cisplatin 75 mg/m(2 ) IV on day 1 , followed by oral etoposide 200 mg/m(2 ) daily on days 2 to 4 . The CEV group received five courses of epirubicin 50 mg/m(2 ) , cyclophosphamide 1,000 mg/m(2 ) , and vincristine 2 mg , all IV on day 1 . In addition , LD patients received thoracic radiotherapy concurrent with chemotherapy cycle 3 , and those achieving complete remission during the treatment period received prophylactic cranial irradiation . RESULTS The treatment groups were well balanced with regard to age , sex , and prognostic factors such as weight loss , and performance status . The 2- and 5-year survival rates in the EP arm ( 14 % and 5 % , P = .0004 ) were significantly higher compared with those in the CEV arm ( 6 % and 2 % ) . Among LD patients , median survival time was 14.5 months versus 9.7 months in the EP and CEV arms , respectively ( P = .001 ) . The 2- and 5-year survival rates of 25 % and 10 % in the EP arm compared with 8 % and 3 % in the CEV arm ( P = .0001 ) . For ED patients , there was no significant survival difference between the treatment arms . Quality -of-life assessment s revealed no major differences between the r and omized groups . CONCLUSION EP is superior to CEV in LD-SCLC patients . In ED-SCLC patients , the benefits of EP and CEV chemotherapy seem 
    Output:
    
Partial tumour response was greater with the active treatment .
Toxicity was only seen in the chemotherapy group and quality of life was only assessed at the beginning of treatment .
Toxicity was worst in the chemotherapy group ( moderate- quality evidence ) .
Two small RCTs from the 1970s suggest that first-line chemotherapeutic treatment ( based on ifosfamide ) may provide a small survival benefit ( less than three months ) in comparison with supportive care or placebo infusion in patients with advanced SCLC .
However platinum-based combination chemotherapy regimens have been shown to increase complete response rates when compared to non-platinum chemotherapy regimens with no significant difference in survival , and so these are currently the st and ard first-line treatment for patients with SCLC.Second-line chemotherapy at relapse or progression may prolong survival for some weeks in relation to BSC .