***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: LBA1 Background : BEV , a humanized anti-VEGF monoclonal antibody , has demonstrated single-agent activity in patients with recurrent EOC , or PPC . The therapeutic impact of concurrent ± maintenance BEV with st and ard chemotherapy ( CT ) was evaluated in an international , double-blind , placebo-controlled phase III trial . METHODS Eligible patients had newly diagnosed , previously untreated EOC , PPC or FTC following abdominal surgery for staging and maximal effort at tumor debulking ; stage III ( macroscopic residual disease ) or stage IV disease . The r and omly allocated regimens were ( 1 ) CT ( IV paclitaxel 175 mg/m2 + carboplatin AUC 6 cycles 1 - 6 ) + placebo cycles (C)2 - 22 ( R1 ) ( 2 ) CT + concurrent BEV ( 15 mg/kg ) C2 - 6 + placebo C7 - 22 ( R2 ) ( 3 ) CT + concurrent BEV C2 - 6 + maintenance BEV C7 - 22 ( R3 ) Infusions were administered d1 of a 21d cycle . The primary endpoint is progression-free survival ( PFS ) ( radiographic , CA125 , clinical criteria or death ) ; secondary endpoints include overall survival , safety , and QoL.  RESULTS 1,873 patients , median age 60 , were enrolled from 9/05 - 6/09 . Stage III optimally debulked ( 34 % ) , stage III sub-optimally debulked ( 40 % ) , and stage IV ( 26 % ) patients were similarly distributed in each treatment group . Grade 3 - 4 hypertension was reported in 1.6 % ( R1 ) , 5.4 % ( R2 ) , and 10.0 % ( R3 ) . Grade ≥ 3 GI perforation , hemorrhage or fistula occurred in 0.8 % ( R1 ) , 2.6 % ( R2 ) and 2.3 % ( R3 ) . Relative to R1 , the hazard of first progression or death for R2 was 0.908 ( 95 % CI : 0.795 - 1.04 , p=0.16 ) and for R3 was 0.717 ( 95 % CI : 0.625 - 0.824 , p<0.0001 ) . CONCLUSIONS This study demonstrates that front-line treatment of EOC , PPC , and FTC patients  with CT plus concurrent and maintenance BEV  prolongs PFS . This is the first anti-angiogenic agent to demonstrate benefit in this population . [ Table : see text ] BACKGROUND AND OBJECTIVES Hypertension and proteinuria are common but poorly understood renal toxicities of vascular endothelial growth factor ( VEGF ) receptor signaling pathway inhibitors . In this phase II study of cediranib ( AZD2171 ) for recurrent epithelial ovarian cancer , the time course and severity of BP changes and proteinuria were characterized . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS 46 women ages 41 to 77 years were treated with cediranib . 26 % had baseline hypertension .  Twice-daily BP was recorded . Urinalyses were performed every 2 weeks , and in some patients proteinuria was further quantified . RESULTS 31 women ( 67 % ) developed hypertension by day 3 ; 87 % by the end of the study . 43 % developed grade > or =3 hypertension . Mean systolic BP increase over 3 days was 18 mmHg . Women above the mean age ( > or = 57 years ) had a larger rise in systolic BP by day 3 ( 15.9 versus 7.0 mmHg ) . 14 women developed proteinuria .  There was a dose response ( 45 versus 30 mg daily ) . Proteinuria also developed rapidly , with 7 of 14 women developing proteinuria within 2 weeks . Only 7 of 20 women who developed grade 3 hypertension developed proteinuria . CONCLUSIONS Cediranib induced a rapid but variable rise in BP within 3 days of initiation in most patients . Proteinuria was common and also developed rapidly . The rapid development of hypertension suggests that acute inhibition of VEGF-dependent vasodilation might explain the BP rise with VEGF inhibitors . Clinicians must be vigilant in early detection and management of toxicities of this exp and ing drug class , especially in older patients 5501 Background : BIBF 1120 is a new targeted therapeutic agent for maintenance therapy in OC . It is a unique triple angiokinase inhibitor , targeting 3 receptor classes involved in the formation of blood vessels ( VEGFR , PDGFR , and FGFR ) . METHODS Continuous BIBF 1120 ( 250 mg , oral , twice daily ) for up to 9 months ( mo ) was compared with placebo in a novel application of a r and omized double-blind trial in pts who responded to their last ( at least second line ) chemotherapy .  The primary endpoint , progression-free survival at 36 weeks , was confirmed by CT assessment , performed at 12-week intervals . RESULTS 84 pts were r and omized ( 44 BIBF 1120 ; 40 placebo ) , mean age 60y ( range 27 - 76 ) . All had responded according to GCIG criteria .  Treatment-free interval  before prior chemotherapy was < 6 mo for 41 % and 6 - 12 mo for 59 % of pts . Median treatment duration was 116 days ( d ) , range , 2 - 281d ( BIBF 1120 ) and 101 d , 2 - 239d ( placebo ) . Five BIBF 1120 pts completed 9 mo of treatment vs 0 placebo pts . The 36-wk PFS rates ( 95 % confidence interval [ CI ] ) were 15.6 % ( 3.8 , 27.3 ) for BIBF 1120 and 2.9 % ( 0.0 , 8.4 ) for placebo . Although the trial was not powered for a direct comparison , the PFS hazard ratio was 0.68 ( 95 % CI : 0.42 , 1.09 ) . Median time to RECIST progression ( mo ) was 4.8 for BIBF 1120 , and 2.8 for placebo . There were no deaths during treatment . Grade 3 and 4 adverse events ( AE ) were seen in 54 and 7 % ( BIBF 1120 ) and 25 and 3 % ( placebo ) of pts . Expected gastrointestinal toxicities occurred slightly more frequently in the BIBF 1120 arm ( 16 vs 10 % , all gd 3 ; no gd 4 events ) . Elevated liver enzymes occurred in 43 % ( BIBF 1120 ) vs. 6.3 % ( placebo ) . CONCLUSIONS Our trial suggests that maintenance BIBF 1120 could delay disease progression in OC pts who had previously responded to chemotherapy . A large phase III trial is needed to confirm the efficacy of this drug . [ Table : see text ] PURPOSE Vascular endothelial growth factor ( VEGF ) plays an important role in the biology of ovarian cancer ( OC ) . Inhibitors of VEGF suppress tumor growth in OC models . Metronomic chemotherapy , defined as frequent administration of low doses of cytotoxic chemotherapy , suppresses tumor growth , possibly by inhibiting angiogenesis . A phase II trial was conducted to evaluate the antitumor activity and adverse effects of bevacizumab and metronomic oral cyclophosphamide in women with recurrent OC . PATIENTS AND METHODS Patients with measurable disease and prior treatment with a platinum-containing regimen were eligible . Up to two different regimens for recurrent disease were allowed . Treatment consisted of bevacizumab 10 mg/kg intravenously every 2 weeks and oral cyclophosphamide 50 mg/d . The primary end point was progression-free survival at 6 months . Plasma levels of VEGF , E-selectin , and thrombospondin-1 were obtained serially . RESULTS Seventy patients were enrolled . The probability of being alive and progression free at 6 months was 56 % ( + /- 6 % SE ) . A partial response was achieved in 17 patients ( 24 % ) . Median time to progression and survival were 7.2 and 16.9 months , respectively . The most common serious toxicities were hypertension , fatigue , and pain . Bevacizumab-related toxicities included four episodes of gastrointestinal perforation or fistula , two episodes each of CNS ischemia and pulmonary hypertension , and one episode each of gastrointestinal bleeding and wound healing complication . There were three treatment-related deaths . Levels of VEGF , E-selectin , and thrombospondin-1 were not associated with clinical outcome . CONCLUSION The combination of bevacizumab and metronomic cyclophosphamide is active in recurrent OC . Further study of this combination is warranted Background : With its potent inhibitory effects against Raf-1 kinase and vascular endothelial growth factor receptor-2 , sorafenib is a novel oral anticancer agent targeting signal transduction and angiogenic pathways . This study is design ed to combine sorafenib and gemcitabine due to their compatibility in pre clinical models and nonoverlapping clinical toxicities . Experimental Design : An initial dose-escalation part of the study enrolled patients with advanced solid tumors , followed by an exp and ed cohort at the recommended dose for patients with advanced unresectable or metastatic pancreatic cancer .  Sorafenib is administered continuously , whereas gemcitabine is given at 1,000 mg/m2 weekly × 7 followed by 1 rest week , then weekly × 3 every 4 weeks . Results : Forty-two patients have been enrolled overall , including 19 in the dose-escalation part and 23 in the extended pancreatic cancer cohort . Demographics were as follows : male-to-female ratio = 26:16 ; median age = 61 years ( range 39 - 83 years ) ; Eastern Cooperative Oncology Group performance status 0:1:2 ratio = 16:21:5 . The recommended dose of this combination is sorafenib 400 mg twice daily and gemcitabine 1,000 mg/m2 . The most frequent grade 3 or 4 adverse events of all causalities were thrombocytopenia ( 28.6 % ) , lymphopenia ( 21.4 % ) , lipase elevation ( 19 % ) , neutropenia ( 16.7 % ) , and fatigue ( 14.3 % ) . Antitumor activity was observed in both groups , with 2 ( 10.5 % ) confirmed partial responses in ovarian cancer and 12 patients ( 63.2 % ) with disease stabilization in the dose-escalation part ; 13 patients ( 56.5 % ) achieved disease stabilization in the pancreatic cohort . There was no consistent pharmacokinetic drug-to-drug interaction between sorafenib and gemcitabine . Conclusions : Sorafenib and gemcitabine are well tolerated in combination ; further evaluations in pancreatic and ovarian cancers are warranted BACKGROUND Recurrent platinum-resistant ovarian cancer usually has a poor outcome with conventional chemotherapeutic therapy and new treatment modalities are warranted . This phase II study was conducted to evaluate sunitinib , an oral antiangiogenic multitargeted tyrosin kinase inhibitor , in this setting . MATERIAL AND METHODS The primary end point of this r and omized phase II trial was the objective response rate according to RECIST criteria and /or Gynecologic Cancer InterGroup CA125 response criteria to sunitinib in patients with recurrent platinum-resistant ovarian cancer who were pretreated with up to three chemotherapies . A selection design was employed to compare two schedules of sunitinib ( arm 1 : 50 mg sunitinib daily orally for 28 days followed by 14 days off drug ; and arm 2 : 37.5 mg sunitinib administered daily continuously ) . RESULTS Of 73 patients enrolled , 36 patients were r and omly allocated to the noncontinuous treatment arm ( arm 1 ) and 37 patients were r and omly allocated to the continuous treatment arm ( arm 2 ) . The mean age was 58.8 and 58.5 years , respectively . We observed six responders ( complete response + partial response ) in arm 1 ( 16.7 % ) and 2 responders in arm 2 ( 5.4 % ) . The median progression-free survival ( arm 1 : 4.8 [ 2.9 - 8.1 ] months ; arm 2 : 2.9 [ 2.9 - 5.1 ] months ) and the median overall survival ( arm 1 : 13.6 [ 7.0 - 23.2 ] months ; arm 2 : 13.7 [ 8.4 - 25.6 ] months ) revealed no significant difference . Adverse events included fatigue as well as cardiovascular , gastrointestinal and abdominal symptoms , hematologic and hepatic laboratory abnormalities . Pattern and frequency of adverse events revealed no substantial differences between both treatment groups . CONCLUSIONS Sunitinib treatment is feasible and moderately active in relapsed platinum-resistant ovarian cancer . The noncontinu 
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However , there is currently no evidence that angiogenesis inhibitors improve OS , nor is there enough evidence to justify the routine use of angiogenesis inhibitors in treating women with ovarian cancer .