***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: Purpose Treating small-cell lung cancer ( SCLC ) remains a therapeutic challenge . Experimental studies show that statins exert additive effects with agents , such as cisplatin , to impair tumor growth , and observational studies suggest that statins combined with anticancer therapies delay relapse and prolong life in several cancer types . To our knowledge , we report the first large , r and omized , placebo-controlled , double-blind trial of a statin with st and ard-of-care for patients with cancer , specifically SCLC . Patients and Methods Patients with confirmed SCLC ( limited or extensive disease ) and performance status 0 to 3 were r and omly assigned to receive daily pravastatin 40 mg or placebo , combined with up to six cycles of etoposide plus cisplatin or carboplatin every 3 weeks , until disease progression or intolerable toxicity . Primary end point was overall survival ( OS ) , and secondary end points were progression-free survival ( PFS ) , response rate , and toxicity . Results Eight hundred forty-six patients from 91 United Kingdom hospitals were recruited . The median age of recruited patients was 64 years of age , 43 % had limited disease , and 57 % had extensive disease . There were 758 deaths and 787 PFS events . No benefit was found for pravastatin , either in all patients or in several subgroups . For pravastatin versus placebo , the 2-year OS rate was 13.2 % ( 95 % CI , 10.0 to 16.7 ) versus 14.1 % ( 95 % CI , 10.9 to 17.7 ) , respectively , with a hazard ratio of 1.01 ( 95 % CI , 0.88 to 1.16 ; P = .90 . The median OS was 10.7 months v 10.6 months , respectively . The median PFS was 7.7 months v 7.3 months , respectively . The median OS  ( pravastatin v placebo ) was 14.6 months in both groups for limited disease and 9.1 months versus 8.8 months , respectively , for extensive disease . Adverse events were similar between groups . Conclusion Pravastatin 40 mg combined with st and ard SCLC therapy , although safe , does not benefit patients . Our conclusions are the same as those found in all four much smaller , r and omized , placebo-controlled trials specifically design ed to evaluate statin therapy in patients with cancer Abstract Background Statins have potential antineoplastic properties via arrest of cell-cycle progression and induction of apoptosis . A previous study demonstrated in vitro and in vivo antineoplastic synergism between statins and gemcitabine . The present r and omized , double-blinded , phase II trial compared the efficacy and safety of gemcitabine plus simvastatin ( GS ) with those of gemcitabine plus placebo ( GP ) in patients with locally advanced and metastatic pancreatic cancer . Methods Patients were r and omly assigned to receive a 3-week regimen with GS ( gemcitabine 1,000 mg/m2 on days 1 , 8 , and 15 plus simvastatin 40 mg once daily ) or GP ( gemcitabine 1,000 mg/m2 on days 1 , 8 , and 15 plus placebo ) . The primary end point was time to progression ( TTP ) . Results Between December 2008 and April 2012 , 114 patients were enrolled .  The median TTP was not significantly different between the two arms , being 2.4 months ( 95 % CI 0.7–4.1 months ) and 3.6 months ( 95 % CI 3.1–4.1 months ) in the GS and GP arms , respectively ( P = 0.903 ) . The overall disease control rate was 39.7 % ( 95 % CI 12.2–33.8 % ) and 57.1 % ( 95 % CI 19.8–44.2 % ) in the GS and GP arms , respectively ( P = 0.09 ) . The 1-year expected survival rates were similar ( 27.7 and 31.7 % in the GS and GP arms , respectively ; P = 0.654 ) . Occurrence of grade 3 or 4 adverse events was similar in both arms , and no patients had rhabdomyolysis . Conclusions Adding low-dose simvastatin to gemcitabine in advanced pancreatic cancer does not provide clinical benefit , although it also does not result in increased toxicity . Given the emerging role of statins in overcoming resistance to anti-EGFR treatment , further studies are justified to evaluate the efficacy and safety of combined simvastatin and anti-EGFR agents , such as erlotinib or cetuximab , plus gemcitabine for treating advanced pancreatic cancer Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Chemotherapy is not effective for hepatocellular carcinoma ( HCC ) . HMG-CoA redutase inhibitors have cytostatic activity for cancer cells , but their clinical usefulness is unknown . To investigate whether pravastatin , a potent HMG-CoA reductase inhibitor , prolongs survival in patients with advanced HCC , this r and omized controlled trial was conducted between February 1990 and February 1998 at Osaka University Hospital . 91 consecutive patients < 71 years old ( mean age 62 ) with unresectable HCC were enroled in this study . 8 patients were withdrawn because of progressive liver dysfunction ; 83 patients were r and omized to st and ard treatment with or without pravastatin . All patients underwent transcatheter arterial embolization ( TAE ) followed by oral 5-FU 200 mg–1d for 2 months . Patients were then r and omly assigned to control ( n = 42 ) and pravastatin ( n = 41 ) groups . Pravastatin was administered at a daily dose of 40 mg . The effect of pravastatin on tumour growth was assessed by ultrasonography . Primary endpoint was death due to progression of HCC . The duration of pravastatin administration was 16.5 ± 9.8 months ( mean ± SD ) . No patients in either group were lost to follow-up . Median survival was 18 months in the pravastatin group versus 9 months in controls ( P = 0.006 ) . The Cox proportional hazards model showed that pravastatin was a significant factor contributing to survival . Pravastatin prolonged the survival of patients with advanced HCC , suggesting its value for adjuvant treatment . © 2001 Cancer Research Purpose : To evaluate the efficacy and safety of gefitinib plus simvastatin ( GS ) versus gefitinib alone ( G ) in previously treated patients with advanced non – small cell lung cancer ( NSCLC ) . Experimental Design : Between May 2006 and September 2008 , 106 patients ( 51 % men , 75 % adenocarcinoma , 50 % never smoker ) were r and omly assigned to G alone ( 250 mg/d , n = 54 ) or GS ( 250 and 40 mg/d , respectively , n = 52 ) . One cycle was 4 weeks of treatment . Therapy was continued until disease progression or intolerable toxicity was observed . The primary endpoint was response rate ( RR ) . Secondary endpoints included toxicity , progression-free survival ( PFS ) , and overall survival ( OS ) . Results : The RR was 38.5 % ( 95 % CI , 25.3–51.7 ) for GS and 31.5 % ( 95 % CI , 19.1–43.9 ) for G. The median PFS was 3.3 months [ M ] ( 95 % CI , 1.4–5.2 M ) for GS and 1.9 M ( 95 % CI , 1.0–2.8 M ) for G. The median OS was 13.6 M ( 95 % CI , 7.1–20.1 M ) for GS and 12.0 M ( 95 % CI , 7.8–16.2 M ) for G. In exploratory subgroup analysis , GS showed higher RR ( 40 % vs. 0 % , P = 0.043 ) and longer PFS ( 3.6 M vs. 1.7 M , P = 0.027 ) compared with G alone in patients with wild-type epidermal growth factor receptor ( EGFR ) nonadenocarcinomas .  Adverse events in both arms were generally mild and mainly consisted of skin rashes . Conclusions : Although no superiority of GS to G was demonstrated in this unselected NSCLC population , GS showed higher RR and longer PFS compared with G alone in patients with wild-type EGFR nonadenocarcinomas .  Simvastatin may improve the efficacy of gefitinib in that subgroup of gefitinib-resistant NSCLC patients . Clin Cancer Res ; 17(6 ) ; 1553–60 . © 2011 AACR Purpose This phase II study examined whether the addition of simvastatin to afatinib provides a clinical benefit compared with afatinib monotherapy in previously treated patients with nonadenocarcinomatous non-small cell lung cancer ( NA-NSCLC ) . Material s and Methods Patients with advanced NA-NSCLC who progressed after one or two chemotherapy regimens were r and omly assigned to a simvastatin ( 40 mg/day ) plus afatinib ( 40 mg/day ) ( AS ) arm or to an afatinib ( A ) arm . The primary endpoint was response rate ( RR ) . Results Sixty-eight patients were enrolled ( 36 in the AS arm and 32 in the A arm ) . The RR was 5.7 % ( 95 % confidence interval [ CI ] , 0.7 to 19.2 ) for AS and 9.4 % ( 95 % CI , 2.0 to 25.0 ) for A ( p=0.440 ) . In arms AS and A , the median progression-free survival ( PFS ) was 1.0 versus 3.6 months ( p=0.240 ) and the overall survival was 10.0 months versus 7.0 months ( p=0.930 ) , respectively . Skin rash , stomatitis , and diarrhea were the most common adverse events in both arms . More grade 3 or 4 diarrhea was observed in arm A ( 18.8 % vs. 5.6 % in arm AS ) . In all patients , the median PFS for treatment including afatinib was not correlated with the status of epidermal growth factor receptor ( EGFR ) mutation ( p=0.122 ) , EGFR fluorescence in situ hybridization ( p=0.944 ) , or EGFR immunohistochemistry ( p=0.976 ) . However , skin rash severity was significantly related to the risk of progression for afatinib ( hazard ratio for skin rash grade ≥ 2 vs. grade < 2 , 0.44 ; 95 % CI , 0.25 to 0.78 ; p=0.005 ) . Conclusion There were no significant differences in the efficacy between AS and A arms in patients with NA-NSCLC BACKGROUND Previous trials have shown that the use of statins to lower cholesterol reduces the risk of cardiovascular events among persons without cardiovascular disease . Those trials have involved persons with elevated lipid levels or inflammatory markers and involved mainly white persons . It is unclear whether the benefits of statins can be extended to an intermediate-risk , ethnically diverse population without cardiovascular disease . METHODS In one comparison from a 2-by-2 factorial trial , we r and omly assigned 12,705 participants in 21 countries who did not have cardiovascular disease and were at intermediate risk to receive rosuvastatin at a dose of 10 mg per day or placebo . The first co primary outcome was the composite of death from cardiovascular causes , nonfatal myocardial infa rct ion , or nonfatal stroke , and the second co primary outcome additionally included revascularization , heart failure , and resuscitated cardiac arrest . The median follow-up was 5.6 years . RESULTS The overall mean low-density lipoprotein cholesterol level was 26.5 % lower in the rosuvastatin group than in the placebo group . The first co primary outcome occurred in 235 participants ( 3.7 % ) in the rosuvastatin group and in 304 participants ( 4.8 % ) in the placebo group ( hazard ratio , 0.76 ; 95 % confidence interval [ CI ] , 0.64 to 0.91 ; P=0.002 ) . The results for the second co primary outcome were consistent with the results for the first ( occurring in 277 participants [ 4.4 % ] in the rosuvastatin group and in 363 participants [ 5.7 % ] in the placebo group ; hazard ratio , 0.75 ; 95 % CI , 0.64 to 0.88 ; P<0.001 ) . The results were also consistent in subgroups defined according to cardiovascular risk at baseline , lipid level , C-reactive protein level , blood pressure , and race or ethnic group . In the rosuvastatin group , there was no excess of diabetes or cancers , but there was an excess of cataract surgery ( in 3.8 % of the participants , vs. 3.1 % in the placebo group ; P=0.02 ) and muscle symptoms ( in 5.8 % of the participants , vs. 4.7 % in the placebo group ; P=0.0 
    Output:
    
In patients with advanced cancer and a prognosis < 2 years , the addition of statins to st and ard anti-cancer therapy does not appear to improve overall survival or progression-free survival .