***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: BACKGROUND Angiogenesis plays a role in the biology of ovarian cancer . We examined the effect of bevacizumab , the vascular endothelial growth factor inhibitor , on survival in women with this disease . METHODS We r and omly assigned women with ovarian cancer to  carboplatin  ( area under the curve , 5 or 6 ) and paclitaxel ( 175 mg per square meter of body-surface area ) , given every 3 weeks for 6 cycles , or to this regimen plus bevacizumab ( 7.5 mg per kilogram of body weight ) , given concurrently every 3 weeks for 5 or 6 cycles and continued for 12 additional cycles or until progression of disease . Outcome measures included progression-free survival , first analyzed per protocol and then up date d , and interim overall survival . RESULTS A total of 1528 women from 11 countries were r and omly assigned to one of the two treatment regimens . Their median age was 57 years ; 90 % had epithelial ovarian cancer , 69 % had a serous histologic type , 9 % had high-risk early-stage disease , 30 % were at high risk for progression , and 70 % had stage IIIC or IV ovarian cancer .  Progression-free survival ( restricted mean ) at 36 months was 20.3 months with st and ard therapy , as compared with 21.8 months with st and ard therapy plus bevacizumab ( hazard ratio for progression or death with bevacizumab added , 0.81 ; 95 % confidence interval , 0.70 to 0.94 ; P=0.004 by the log-rank test ) . Nonproportional hazards were detected ( i.e. , the treatment effect was not consistent over time on the hazard function scale ) ( P<0.001 ) , with a maximum effect at 12 months , coinciding with the end of planned bevacizumab treatment and diminishing by 24 months . Bevacizumab was associated with more toxic effects ( most often hypertension of grade 2 or higher ) ( 18 % , vs. 2 % with chemotherapy alone ) . In the up date d analyses , progression-free survival ( restricted mean ) at 42 months was 22.4 months without bevacizumab versus 24.1 months with bevacizumab ( P=0.04 by log-rank test ) ; in patients at high risk for progression , the benefit was greater with bevacizumab than without it , with progression-free survival ( restricted mean ) at 42 months of 14.5 months with st and ard therapy alone and 18.1 months with bevacizumab added , with respective median overall survival of 28.8 and 36.6 months . CONCLUSIONS Bevacizumab improved progression-free survival in women with ovarian cancer . The benefits with respect to both progression-free and overall survival were greater among those at high risk for disease progression . ( Funded by Roche and others ; ICON7 Controlled-Trials.com number , IS RCT N91273375 . ) BACKGROUND Targeting of VEGF is a potential therapeutic option in patients with malignant ovarian ascites . We present the final results of a multicentre study of the efficacy and safety of aflibercept , a potent inhibitor of both VEGF and placental growth factor , in the treatment of malignant ascites . METHODS In this double-blind , placebo-controlled , parallel-group , phase 2 study , patients with advanced chemoresistant ovarian cancer and recurrent symptomatic malignant ascites were r and omly assigned ( 1:1 ) via an interactive voice response system to either intravenous aflibercept ( 4 mg/kg every 2 weeks ) or placebo , stratified by interval of time ( ≤ 2 weeks vs > 2 weeks ) between the two most recent paracenteses before r and omisation . Patients participated in the double-blind period ( during which patients , investigators , and sponsor personnel were masked to treatment assignment ) until they had a repeat paracentesis and for at least 60 days , and could also participate in an optional open-label period during which all patients received aflibercept . The primary efficacy endpoint was time to repeat paracentesis based on response during the double-blind period alone , and was analysed in the intention-to-treat population with censoring of patients who did not have a repeat paracentesis as of the last day of the double-blind period . Safety analyses included both double-blind and open-label periods . This study is registered at Clinical Trials.gov , number NCT00327444 . FINDINGS 55 patients with a median of four ( range two to 11 ) previous lines of chemotherapy were r and omly assigned to receive placebo ( n=26 ) or aflibercept ( n=29 ) . Mean time to repeat paracentesis was significantly longer with aflibercept than with placebo ( 55·1 [ SE 7·3 ] vs 23·3 [ 7·7 ] days ; difference 31·8 days , 95 % CI 10·6 - 53·1 ; p=0·0019 ) . In the aflibercept group , two patients did not need a repeat paracentesis during 6 months of double-blind treatment . The most common grade 3 or 4 treatment-emergent adverse events were dyspnoea ( six [ 20 % ] aflibercept vs two [ 8 % ] placebo ) , fatigue or asthenia ( four [ 13 % ] vs 11 [ 44 % ] ) , and dehydration ( three [ 10 % ] vs three [ 12 % ] ) . The frequency of fatal gastrointestinal events was higher with aflibercept ( three intestinal perforations ) than with placebo ( one intestinal fistula leading to sepsis ) . INTERPRETATION This study shows the effectiveness of VEGF blockade in the reduction of malignant ascites , but confirms the significant clinical risk of fatal bowel perforation in this population of patients with very advanced cancer .  VEGF blockade should be used with caution in advanced ovarian cancer with abdominal carcinomatosis , and the benefit-risk balance should be thoroughly discussed for each patient . FUNDING Sanofi Oncology PURPOSE This r and omized , multicenter , blinded , placebo-controlled phase III trial tested the efficacy and safety of bevacizumab ( BV ) with gemcitabine and carboplatin ( GC ) compared with GC in platinum-sensitive recurrent ovarian , primary peritoneal , or fallopian tube cancer ( ROC ) . PATIENTS AND METHODS Patients with platinum-sensitive ROC ( recurrence ≥ 6 months after front-line platinum-based therapy ) and measurable disease were r and omly assigned to GC plus either BV or placebo ( PL ) for six to 10 cycles . BV or PL , respectively , was then continued until disease progression . The primary end point was progression-free survival ( PFS ) by RECIST ; secondary end points were objective response rate , duration of response ( DOR ) , overall survival , and safety . RESULTS Overall , 484 patients were r and omly assigned . PFS for the BV arm was superior to that for the PL arm ( hazard ratio [ HR ] , 0.484 ; 95 % CI , 0.388 to 0.605 ; log-rank P < .0001 ) ; median PFS was 12.4 v 8.4 months , respectively . The objective response rate ( 78.5 % v 57.4 % ; P < .0001 ) and DOR ( 10.4 v 7.4 months ; HR , 0.534 ; 95 % CI , 0.408 to 0.698 ) were significantly improved with the addition of BV . No new safety concerns were noted . Grade 3 or higher hypertension ( 17.4 % v < 1 % ) and proteinuria ( 8.5 % v < 1 % ) occurred more frequently in the BV arm . The rates of neutropenia and febrile neutropenia were similar in both arms . Two patients in the BV arm experienced GI perforation after study treatment discontinuation . CONCLUSION GC plus BV followed by BV until progression result ed in a statistically significant improvement in PFS compared with GC plus PL in platinum-sensitive ROC PURPOSE Inhibiting angiogenesis is one of the most promising avenues for new therapies for ovarian cancer . We investigated the efficacy and safety of a novel agent , BIBF 1120 , a triple angiokinase inhibitor , after chemotherapy for relapsed disease . PATIENTS AND METHODS We conducted a r and omized , double-blind , controlled phase II trial in 83 patients who had just completed chemotherapy for relapsed ovarian cancer , with evidence of response , but at high risk of further early recurrence . The patients were r and omly assigned to receive maintenance therapy using BIBF 1120 250 mg or placebo , twice per day , continuously for 36 weeks . End points were progression-free survival ( PFS ) , toxicity , and overall survival . RESULTS Thirty-six-week PFS rates were 16.3 % and 5.0 % in the BIBF 1120 and placebo groups , respectively ( hazard ratio , 0.65 ; 95 % CI , 0.42 to 1.02 ; P = .06 ) . Four patients continued on BIBF 1120 , including two patients for another year or more . The proportion of patients with any grade 3 or 4 adverse events was similar between the groups ( 34.9 % for BIBF 1120 v 27.5 % for placebo ; P = .49 ; mostly grade 3 ) . However , more patients on BIBF 1120 experienced diarrhea , nausea , or vomiting ( mainly grade 1 or 2 and no grade 4 ) . There was a higher rate of grade 3 or 4 hepatotoxicity in patients on BIBF 1120 ( 51.2 % ) compared with patients on placebo ( 7.5 % ; P < .001 ) , but this was rarely of clinical significance , and patients continued with the trial treatment . A single-level dose reduction to 150 mg was made in 15 patients , all on active drug . CONCLUSION BIBF 1120 is well tolerated and associated with a potential improvement in PFS . The observed treatment effect is sufficient to justify further study within a large phase III trial Purpose : This phase II trial evaluated bevacizumab plus erlotinib in platinum-resistant ovarian cancer ; exploratory biomarker analyses , including that of tumor vascular endothelial growth factor A ( VEGF-A ) , were also done . Experimental Design : Forty heavily pretreated patients received erlotinib (  150 mg/d orally ) and bevacizumab ( 10 mg/kg i.v . ) every 2 weeks until disease progression . Primary end points were objective response rate and response duration ; secondary end points included progression-free survival ( PFS ) , toxicity , and correlations between angiogenic protein levels , toxicity , and efficacy . Results : Grade 3 toxicities included skin rash ( n = 6 ) , diarrhea ( n = 5 ) , fatigue ( n = 4 ) , and hypertension ( n = 3 ) . Grade 4 toxicities were myocardial infa rct ion ( n = 1 ) and nasal septal perforation ( n = 1 ) . Only one grade 3 fistula and one grade 2 bowel perforation were observed . Nine ( 23.1 % ) of 39 evaluable patients had a response ( median duration , 36.1 + weeks ; one complete response ) , and 10 ( 25.6 % ) patients achieved stable disease , for a disease control rate of 49 % . Median PFS was 4 months , and 6-month PFS was 30.8 % . Biomarker analyses identified an association between tumor cell VEGF-A expression and progression ( P = 0.03 ) ; for every 100-unit increase in the VEGF-A score , there was a 3.7-fold increase in the odds of progression ( 95 % confidence interval , 1.1 - 16.6 ) . Conclusions : Bevacizumab plus erlotinib  in heavily pretreated ovarian cancer patients was clinical ly active and well tolerated . Erlotinib did not seem to contribute to efficacy . Our study raises the intriguing possibility that high levels of tumor cell VEGF-A , capable of both autocrine and paracrine interactions , are associated with resistance to bevacizumab , emphasizing the complexity of the tumor microenvironment . Clin Cancer Res ; 16(21 ) ; 5320–8 . © 2010 AACR 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 
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The type and frequency of bevacizumab-related adverse events was as expected in these studies based on published data .
Promising efficacy data have been published for a number of emerging anti-angiogenic agents in phase III development for advanced ovarian cancer .