***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 
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    ***EXAMPLES*** 
    Input: BACKGROUND It is unknown whether combined chemoradiotherapy improves overall survival in elderly patients with locally advanced non-small-cell lung cancer ( NSCLC ) . The aim of this study was to assess whether radiotherapy plus carboplatin results in longer survival than radiotherapy alone in elderly patients with NSCLC . METHODS This was a r and omised , controlled , phase 3 trial by the Japan Clinical Oncology Group ( JCOG0301 ) . Patients older than 70 years with unresectable stage III NSCLC were r and omly assigned to chemoradiotherapy ( 60 Gy plus concurrent low-dose carboplatin [ 30 mg/m(2 ) per day , 5 days a week for 20 days ] ) or radiotherapy alone , using a minimisation method with biased-coin assignment balancing on Eastern Cooperative Oncology Group ( ECOG ) performance status ( 0 vs 1 vs 2 ) , stage ( IIIA vs IIIB ) , and institution . The primary endpoint was overall survival , which was analysed for the eligible population and stratified by ECOG performance status , stage , and institution . The trial was stopped early as a result of the second planned interim analysis . This study is registered with UMIN Clinical Trials Registry , number C000000060 , and Clinical Trials.gov , number NCT00132665 . FINDINGS 200 patients were enrolled from Sept 1 , 2003 to May 27 , 2010 : 100 in the chemoradiotherapy group and 100 in the radiotherapy group . The second planned interim analysis was done 10 months after completion of patient accrual . At this time , median follow-up for censored cases was 19·4 months ( IQR 10·3 - 33·5 ) . In accordance with the prespecified stopping rule , the JCOG data and safety monitoring committee recommended early publication of this trial because the difference in overall survival favoured the chemoradiotherapy group . Median overall survival  for the chemoradiotherapy and radiotherapy alone groups were 22·4 months ( 95 % CI 16·5 - 33·6 ) and 16·9 months ( 13·4 - 20·3 ) , respectively ( hazard ratio 0·68 , 95·4 % CI 0·47 - 0·98 , stratified log-rank test one-sided p value=0·0179 ) . More patients had grade 3 - 4 haematological toxic effects  in the chemoradiotherapy group than in the radiotherapy alone group , including leucopenia ( 61 [ 63·5 % ] vs none ) , neutropenia ( 55 [ 57·3 % ] vs none ) , and thrombocytopenia ( 28 [ 29·2 % ] vs two [ 2·0 % ] ) . Grade 3 infection was more common with chemoradiotherapy ( 12 patients [ 12·5 % ] ) than with radiotherapy ( four patients [ 4·1 % ] ) . Incidences of grade 3 - 4 pneumonitis and late lung toxicity were similar between groups . There were seven treatment-related deaths : three of 100 patients ( 3·0 % ) in the chemoradiotherapy group and four of 100 ( 4·0 % ) in the radiotherapy group . INTERPRETATION For a select group of elderly patients with locally advanced NSCLC  , combination chemoradiotherapy provides a clinical ly significant benefit over radiotherapy alone , and should be considered for this population . FUNDING Ministry of Health , Labour , and Welfare of Japan Docetaxel plus prednisone is currently the st and ard first‐line treatment in metastatic castration‐resistant prostate cancer ( mCRPC ) . The aim of this study was to assess the clinical activity and pharmacodynamic/pharmacogenetic profile of docetaxel plus prednisone in combination with metronomic cyclophosphamide in mCRPC patients This phase 1 study evaluated the safety and tolerability of  antiangiogenic therapy using v and etanib and metronomic cyclophosphamide and methotrexate in metastatic breast cancer . Eligible patients had metastatic breast cancer with 0–4 prior chemotherapy regimens . All received cyclophosphamide 50 mg daily , methotrexate 2.5 mg days 1–2 weekly , and v and etanib daily in 3 dose-escalation cohorts : 100 mg ( C1 ) , 200 mg ( C2 ) , and 300 mg ( C3 ) . The primary endpoint was safety and tolerability ; secondary endpoints included response rate and evaluation of platelet-associated proteins .  Twenty three patients were treated and evaluable for toxicity . Common mild toxicities included nausea , vomiting , LFTs abnormalities , fatigue , and rash . Three episodes of dose-limiting toxicity occurred in C3 . In all cohorts , 1/3 of patients required v and etanib dose reduction , and 22 % ended therapy for toxicity . Of the 20 response-evaluable patients , 10 % demonstrated partial response and 15 % stable disease ≥24 weeks . Proteomic analyses demonstrated changes in platelet content of angiogenesis regulators , including vascular endothelial growth factor and platelet factor 4 , with exposure to therapy . This regimen was tolerable at a maximum v and etanib dose of 200 mg ; modest clinical activity was observed in this heavily pretreated population . Changes in the platelet proteome may serve as pharmacodynamic markers of angiogenesis inhibition . Metronomic chemotherapy is an attractive partner with biologics and deserves further study in metastatic breast cancer Background Metronomic oral vinorelbine could be a safe option for elderly patients with advanced non small cell lung cancer ( NSCLC ) . Metronomic administration of chemotherapy leads to a cytostatic action shifting treatment target from cancer cell to tumor angiogenesis . Methods 43 chemotherapy naive elderly ( ≥70 yrs ) PS 0 - 2 patients with stage IIIB-IV NSCLC were prospect ively recruited . Median age was 80 yrs ( M/F 36/7 ) with predominantly squamous histology . PS distribution was 0 - 1(16)/2(27 ) with a median of 3 serious co-morbid illnesses . Study treatment consisted of oral vinorelbine 50 mg three times weekly ( Monday-Wednesday-Friday ) continuously until disease progression , unacceptable toxicity or patient refusal . Primary endpoints were overall response rate ( ORR ) , clinical benefit ( CB – disease response plus disease stabilization > 12 weeks ) and safety . Health-related QoL ( HRQoL ) was also assessed with FACT-L V4 scoring question naire . We conducted an exploratory time-course analysis of VEGF and thrombospondin-1 ( TSP1 ) serum levels in a subgroup of patients . Results Patients received a median of 5 ( range 1 - 21 ) cycles with a total of 272 cycles delivered . ORR was 18.6 % with 7 partial and 1 complete responses ; 17/43 experienced stable disease lasting more than 12 weeks leading to an overall CB of 58.1 % . Median time to progression was 5 ( range 2 - 21 ) and median overall survival 9 ( range 3 - 29 ) months . Treatment was well tolerated with rare serious toxicity . Regardless of severity main toxicities observed were anemia in 44 % , fatigue in 32.4 % , and diarrhoea 10.5 % . FACT-L v4 scores did not significantly vary during treatment . Baseline VEGF levels were lower and showed a rapid increase during treatment in non-responders pts only while TSP1 levels did not change . Conclusions Metronomic oral vinorelbine is safe in elderly patients with advanced NSCLC with an interesting activity mainly consisting in long-term disease stabilization coupled with an optimal patient compliance ( Eudra-CT 2010 - 018762 - 23 , AIFA OSS on 26 February 2010 ) Importance Although oral metronomic chemotherapy is often used in progressive pediatric solid malignant tumors , a literature review reveals that only small single-arm retrospective or phase 1 and 2 studies have been performed . Skepticism abounds because of the lack of level 1 evidence . Objectives To compare the effect of metronomic chemotherapy on progression-free survival ( PFS ) with that of placebo in pediatric patients with primary extracranial , nonhematopoietic solid malignant tumors that progress after at least 2 lines of chemotherapy . Design , Setting , and Participants A double-blinded , placebo-controlled  r and omized clinical trial was conducted from October 1 , 2013 , through December 31 , 2015 , at the cancer center at All India Institute of Medical Sciences in children aged 5 to 18 years with primary extracranial , nonhematopoietic solid malignant tumors that progressed after at least 2 lines of chemotherapy and had no further curative options . Interventions One arm received a 4-drug oral metronomic regimen of daily celecoxib and thalidomide with alternating periods of etoposide and cyclophosphamide , whereas the other arm received placebo . Disease status was assessed at baseline , 9 weeks , 18 weeks , and 27 weeks or at clinical progression . Main Outcomes and Measures The primary end point was PFS as defined by the proportion of patients without disease progression at 6 months , and PFS duration and overall survival ( OS ) were secondary end points . Results A total of 108 of the 123 patients screened were enrolled , with 52 r and omized to the placebo group ( median age , 15 years ; 40 male [ 76.9 % ] ) and 56 to the metronomic chemotherapy group ( median age , 13 years ; 42 male [ 75.0 % ] ) . At a median follow-up of 2.9 months , 100 % of the patients had disease progression by 6 months in the placebo group vs 96.4 % in the metronomic chemotherapy group ( P = .24 ) . Median PFS and OS in the 2 groups was similar ( hazard ratio [ HR ] , 0.69 ; 95 % CI , 0.47 - 1.03 [ P = .07 ] for PFS ; and HR , 0.74 ; 95 % CI , 0.50 - 1.09 [ P = .13 ] for OS ) . In post hoc subgroup analysis , cohorts receiving more than 3 cycles ( HR for PFS , 0.46 ; 95 % CI , 0.23 - 0.93 ; P = .03 ) and those without a bone sarcoma ( ie , neither primitive neuroectodermal tumor nor osteosarcoma ) ( HR for PFS , 0.39 ; 95 % CI , 0.18 - 0.81 ; P = .01 ) appeared to benefit from metronomic chemotherapy . Conclusions and Relevance Metronomic chemotherapy does not improve 6-month PFS , compared with placebo , among pediatric patients with extracranial progressive solid malignant tumors . However , patients without bone sarcoma and those able to tolerate therapy for more than 3 cycles ( 9 weeks ) benefit . Trial Registration clinical trials.gov Identifier : NCT01858571 Prognosis of recurrent glioblastoma ( GBM ) is poor with 6-month progression-free survival ( PFS6 ) ranging from 9 to 48 % depending on the treatment regimen and use of anti-angiogenic therapies . We sought to study vorinostat ( VOR ) , a histone deacetylase inhibitor , in combination with bevacizumab ( BEV ) and daily metronomic temozolomide ( TMZ ) in a Phase I/II trial in recurrent high- grade gliomas ( HGGs ) . This was a Phase I/II open-label , single-arm study in recurrent HGG patients . Phase I primary endpoint was to determine the maximum tolerated dose ( MTD ) of VOR with BEV and daily TMZ . Phase II primary endpoint was PFS6 . Regimen was BEV 10 mg/kg iv every 2 weeks , TMZ 50 mg/m2 po daily , and VOR 200 or 400 mg po alternating 7 days on then 7 days off throughout a 28-day cycle . Phase I portion enrolled nine subjects with three receiving VOR 200 mg and 6 receiving VOR 400 mg . With no dose-limiting toxicities ( DLTs ) at 200 mg and one DLT ( thrombocytopenia , Grade 3 ) at 400 mg , the MTD was 400 mg . Phase II portion enrolled 39 GBM subjects , and PFS6 was 53.8 % ( 95 % CI 37.2–67.9 % ) . Of note , 14 subjects had received prior BEV and all had received prior 5-day TMZ . Combination therapy with VOR , BEV , and daily TMZ  was well tolerated and safe . While PFS6 was not statistically improved beyond historical controls , it is important to note that this was a heavily pretreated GBM population and further consideration is warranted in a less pretreated group INTRODUCTION The goal of this study was to explore the efficacy and tolerability of metronomic chemotherapy , a novel anti-angiogenic treatment strategy , in combination with bevacizumab in patients with advanced non-small cell lung cancer ( NSCLC ) . METHODS Subjects with newly diagnosed stage IV NSCLC were treated with 4-week cycles of paclitaxel 80mg 
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Discussion : Most of the studies did not show significantly improved overall survival or progression-free survival .
Therefore , there is no definite evidence on the efficacy of single metronomic dosing and firm evidence of metronomic dosing is still missing .