***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: OBJECTIVES Veliparib ( V ) potentiated therapeutic efficacy of cisplatin ( C ) and etoposide ( E ) in pre clinical models of SCLC . We conducted this phase 1 study to establish the safety of the combination in human subjects . MATERIAL S AND METHODS The study employed the 3 + 3 dose escalation design to establish the safety and recommended phase 2 dose ( RP2D ) of V when combined with fixed doses of C ( 75 mg/m(2 ) on day 1 ) and E ( 100mg/m(2 ) on days 1 - 3 ) in a 21-day cycle . The starting dose of V was 60 mg ( bid days 1 - 7 ) with plan to escalate to 100 mg ( days 1 - 7 ) or de-escalate to 40 mg ( days 1 - 7 ) depending on the dose limiting toxicity ( DLT ) experience during cycle 1 . Patients with treatment-naïve , extensive stage SCLC were included . RESULTS The study enrolled 9 patients : M/F ( 4/5 ) ; median age ( 60 ) ; White/African American ( 8/1 ) . V was tolerated at the 60 mg ( DLT in 0 of 3 patients ) and 100 mg dose ( DLT in 1 of 6 patients ; grade 5 cardiac failure ) . Veliparib at 100 mg in combination with st and ard doses of C and E was established as the RP2D . Grade s 3 - 5 adverse events irrespective of attribution during cycle 1 included : dehydration ( 1 ) , diarrhea ( 1 ) , fatigue ( 1 ) , febrile neutropenia ( 1 ) , heart failure ( 1 ) , leukopenia ( 6 ) , lymphopenia ( 1 ) , nausea ( 2 ) , neutropenia ( 8) , respiratory failure ( 1 ) , and thrombocytopenia ( 2 ) . Investigator-assessed efficacy outcome in 7 evaluable patients were stable disease in 2/7 ( 28.6 % ) , partial response in 4/7 ( 57.1 % ) , and complete response in 1/7 ( 14.3 % ) patients . CONCLUSIONS This study demonstrated the safety of combining veliparib with cisplatin and etoposide in previously untreated SCLC patients Purpose : This phase II study was conducted to assess the efficacy of temozolomide in patients with relapsed small cell lung cancer ( SCLC ) . Experimental Design : Patients with disease progression after one or two prior chemotherapy regimens received temozolomide at 75 mg/m2/d for 21 days of a 28-day cycle . The primary endpoint was the overall response rate [ ORR ; complete response ( CR ) plus partial response ( PR ) ] , which was evaluated separately in sensitive and refractory cohorts . In the available tissue , we assessed O6-methylguanine-DNA methyltransferase ( MGMT ) promoter methylation status by PCR and MGMT expression by immunohistochemistry . Results : Sixty-four patients were accrued : 48 patients in the sensitive cohort and 16 in the refractory group . One CR and 10 PRs were noted in sensitive patients [ ORR , 23 % ; 95 % confidence interval ( CI ) , 12%–37 % ] . Two PRs were seen in the refractory cohort ( ORR , 13 % ; 95 % CI , 2%–38 % ) . As second- and third-line treatment , the ORR was 22 % ( 95 % CI , 9%–40 % ) and 19 % ( 95 % CI , 7%–36 % ) , respectively . Among patients with target brain lesions , 38 % had a CR or PR ( 95 % CI , 14%–68 % ) . Grade ≥3 thrombocytopenia and neutropenia were observed in nine patients ( 14 % ) . A greater number of cases with methylated MGMT had a response compared to those with unmethylated MGMT ( 38 % vs. 7 % ; P = 0.08 ) . Conclusion : Temozolomide has activity in relapsed SCLC , particularly for brain metastases . Response to temozolomide may correlate with MGMT methylation in SCLC . Clin Cancer Res ; 18(4 ) ; 1138–45 . © 2012 AACR BACKGROUND Most patients with extensive stage small-cell lung cancer ( ES-SCLC ) who undergo  chemotherapy , and prophylactic cranial irradiation , have persistent intrathoracic disease . We assessed thoracic radiotherapy for treatment of this patient group . METHODS We did this phase 3 r and omised controlled trial at 42 hospitals : 16 in Netherl and s , 22 in the UK , three in Norway , and one in Belgium . We enrolled patients with WHO performance score 0 - 2 and confirmed ES-SCLC who responded to chemotherapy .  They were r and omly assigned ( 1:1 ) to receive either thoracic radiotherapy ( 30 Gy in ten fractions ) or no thoracic radiotherapy . All underwent prophylactic cranial irradiation . The primary endpoint was overall survival at 1 year in the intention-to-treat population . Secondary endpoints included progression-free survival . This study is registered with the Nederl and s Trial Register , number NTR1527 . FINDINGS We r and omly assigned 498 patients between Feb 18 , 2009 , and Dec 21 , 2012 . Three withdrew informed consent , leaving 247 patients in the thoracic radiotherapy group and 248 in the control group . Mean interval between diagnosis and r and omisation was 17 weeks . Median follow-up was 24 months . Overall survival at 1 year was not significantly different between groups : 33 % ( 95 % CI 27 - 39 ) for the thoracic radiotherapy group versus 28 % ( 95 % CI 22 - 34 ) for the control group ( hazard ratio [ HR ] 0.84 , 95 % CI 0.69 - 1.01 ; p=0.066 ) . However , in a secondary analysis , 2-year overall survival was 13 % ( 95 % CI 9 - 19 ) versus 3 % ( 95 % CI 2 - 8 ; p=0.004 ) . Progression was less likely in the thoracic radiotherapy group than in the control group ( HR 0.73 , 95 % CI 0.61 - 0.87 ; p=0.001 ) . At 6 months , progression-free survival was 24 % ( 95 % CI 19 - 30 ) versus 7 % ( 95 % CI 4 - 11 ; p=0.001 ) . We recorded no severe toxic effects . The most common grade 3 or higher toxic effects were fatigue ( 11 vs 9 ) and dyspnoea ( three vs four ) . INTERPRETATION Thoracic radiotherapy in addition to prophylactic cranial irradiation should be considered for all patients with ES-SCLC who respond to chemotherapy . FUNDING Dutch Cancer Society ( CKTO ) , Dutch Lung Cancer Research Group , Cancer Research UK , Manchester Academic Health Science Centre Trials Coordination Unit , and the UK National Cancer Research Network Hypothesis : To study the progression-free survival ( PFS ) and toxicity with 25- or 250-mg doses of temsirolimus ( CCI-779 ) after induction chemotherapy in patients with extensive small-cell lung cancer . Methods : Patients with either stable or responding disease to four to six cycles of cisplatin or carboplatin plus etoposide or irinotecan  were r and omized between 4 and 8 weeks after completion of induction therapy to receive either 25 or 250 mg of temsirolimus intravenously every week until disease progression . Results : Eighty-seven patients entered between January 2002 and December 2003 , of whom 85 were eligible : 44 received 25 mg ( arm A ) , and 41 received 250 mg ( arm B ) . The overall median follow-up time for all eligible patients was 34.6 months . Median age was 59 years ( range , 39–80 ) ; 42 ( 49.4 % ) were male and 43 ( 50.6 % ) female ; 12.9 % had brain metastases . The overall median and 1-year PFS were 2.2 months ( 95 % confidence interval [ CI ] : 1.8 , 2.9 ) and 4.7 % ( 95 % CI : 0.2 % , 9.2 % ) , respectively . The median PFS ( 95 % CI ) for arm A was 1.9 months ( 1.6 , 2.3 ) ; for arm B , it was 2.5 months ( 1.9 , 3.4 ; p = 0.24 ) . The median overall survival from r and omization was 8 months ( 95 % CI : 6.5 , 9.5 ) . Among the 86 patients with reported  toxicities , 36 ( 42 % ) had grade 3 toxicities , the most common of which were thrombocytopenia , hypophosphatemia , and fatigue , and an additional 12 ( 14 % ) had grade 4 toxicities , the most common of which was neutropenia . No patients experienced lethal toxicities . Conclusion : Temsirolimus ( CCI 779 ) , given at 25 or 250 mg weekly , seemed not to increase the PFS in this patient population PURPOSE This double-blind r and omized phase II trial examined whether v and etanib , an inhibitor of vascular endothelial and epidermal growth factor receptors , could prolong progression-free survival in responding patients with small-cell lung cancer . PATIENTS AND METHODS Eligible patients with complete response ( CR ) or partial response ( PR ) to combination chemotherapy ( + /- thoracic or prophylactic cranial radiation ) received oral v and etanib 300 mg/d or matched placebo .  With 100 patients and 77 events , the study had 80 % power to detect an improvement in median progression-free survival from 4 to 6.5 months ( one-sided , 10%-level test ) . RESULTS Between May 2003 and March 2006 , 107 patients were accrued ; 46 had limited disease and 61 extensive disease . There were fewer patients with a performance status of 0 ( n = 11 v 20 ) , and fewer had CR to initial therapy ( n = 4 v 8) in the v and etanib arm . V and etanib patients had more toxicity and required more dose modifications for gastrointestinal toxicity and rash . Asymptomatic Corrected QT interval ( QTC ) prolongation was observed in eight v and etanib patients . Median progression-free survival for v and etanib and placebo was 2.7 and 2.8 months , respectively ( hazard ratio [ HR ] , 1.01 ; 80 % CI , 0.75 to 1.36 ; one-sided P = .51 ) . Overall survival for v and etanib was 10.6 versus 11.9 months for placebo ( HR , 1.43 ; 80 % CI , 1.00 to 2.05 ; one-sided P = 0.9 ) . In planned subgroup analyses , a significant interaction was noted ( P = .01 ) : limited-stage v and etanib patients had longer overall survival ( HR , 0.45 ; one-sided P = .07 ) and extensive-stage v and etanib patients shorter survival compared with placebo ( HR , 2.27 ; one-sided P = .996 ) . CONCLUSION V and etanib failed to demonstrate efficacy as maintenance therapy for small-cell lung cancer PURPOSE Amrubicin , a third-generation anthracycline and potent topoisomerase II inhibitor , showed promising activity in small-cell lung cancer ( SCLC ) in phase II trials . This phase III trial compared the safety and efficacy of amrubicin versus topotecan as second-line treatment for SCLC . PATIENTS AND METHODS A total of 637 patients with refractory or sensitive SCLC were r and omly assigned at a ratio of 2:1 to 21-day cycles of amrubicin 40 mg/m(2 ) intravenously ( IV ) on days 1 to 3 or topotecan 1.5 mg/m(2 ) IV on days 1 to 5 . Primary end point was overall survival ( OS ) ; secondary end points included overall response rate ( ORR ) , progression-free survival ( PFS ) , and safety . RESULTS Median OS was 7.5 months with amrubicin versus 7.8 months with topotecan ( hazard ratio [ HR ] , 0.880 ; P = .170 ) ; in refractory patients , median OS was 6.2 and 5.7 months , respectively ( HR , 0.77 ; P = .047 ) . Median PFS was 4.1 months with amrubicin and 3.5 months with topotecan ( HR , 0.802 ; P = .018 ) . ORR was 31.1 % with amrubicin and 16.9 % with topotecan ( odds ratio , 2.223 ; P < .001 
    Output:
    
Although limited by the identification of only two trials meeting eligibility criteria and the heterogeneity in radiation dose/fractionation and response to induction required , the pooling of data allows greater precision in the estimate of effect size from thoracic RT and confirms the results of the trials individually .
These aggregate data confirm that consolidative thoracic RT