***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 . ) Investigators should properly calculate sample sizes before the start of their r and omised trials and adequately describe the details in their published report . In these a-priori calculations , determining the effect size to detect -- eg , event rates in treatment and control groups -- reflects inherently subjective clinical judgments . Furthermore , these judgments greatly affect sample size calculations . We question the br and ing of trials as unethical on the basis of an imprecise sample size calculation process . So-called underpowered trials might be acceptable if investigators use method ological rigor to eliminate bias , properly report to avoid misinterpretation , and always publish results to avert publication bias . Some shift of emphasis from a fixation on sample size to a focus on method ological quality would yield more trials with less bias . Unbiased trials with imprecise results trump no results at all . Clinicians and patients deserve guidance now PURPOSE The objective of this study was to compare the efficacy and safety of trabectedin plus pegylated liposomal doxorubicin ( PLD ) with that of PLD alone in women with recurrent ovarian cancer after failure of first-line , platinum-based chemotherapy . PATIENTS AND METHODS Women > or = 18 years , stratified by performance status ( 0 to 1 v 2 ) and platinum sensitivity , were r and omly assigned to receive an intravenous infusion of PLD 30 mg/m(2 ) followed by a 3-hour infusion of trabectedin 1.1 mg/m(2 ) every 3 weeks or PLD 50 mg/m(2 ) every 4 weeks . The primary end point was progression-free survival ( PFS ) by independent radiology assessment . RESULTS Patients ( N = 672 ) were r and omly assigned to trabectedin/PLD ( n = 337 ) or PLD ( n = 335 ) . Median PFS was 7.3 months with trabectedin/PLD v 5.8 months with PLD ( hazard ratio , 0.79 ; 95 % CI , 0.65 to 0.96 ; P = .0190 ) . For platinum-sensitive patients , median PFS was 9.2 months v 7.5 months , respectively ( hazard ratio , 0.73 ; 95 % CI , 0.56 to 0.95 ; P = .0170 ) . Overall response rate ( ORR ) was 27.6 % for trabectedin/PLD v 18.8 % for PLD ( P = .0080 ) ; for platinum-sensitive patients , it was 35.3 % v 22.6 % ( P = .0042 ) , respectively . ORR , PFS , and overall survival among platinum-resistant patients were not statistically different . Neutropenia was more common with trabectedin/PLD .  Grade 3 to 4 transaminase elevations were also more common with the combination but were transient and noncumulative . H and -foot syndrome and mucositis were less frequent with trabectedin/PLD than with PLD alone . CONCLUSION When combined with PLD , trabectedin improves PFS and ORR over PLD alone with acceptable tolerance in the second-line treatment of recurrent ovarian cancer PURPOSE To compare the safety and efficacy of carboplatin and paclitaxel administered with or without the multidrug resistance modulator valspodar ( PSC 833 ) in untreated patients with advanced ovarian or primary peritoneal cancer . PATIENTS AND METHODS Seven hundred sixty-two patients with stage IV or suboptimally debulked stage III ovarian or primary peritoneal cancer were r and omly assigned to receive either valspodar 5 mg/kg every 6 hours for 12 doses , paclitaxel 80 mg/m(2 ) , and carboplatin area under the curve ( AUC ) 6 ( PC-PSC ; n = 381 ) or paclitaxel 175 mg/m(2 ) and carboplatin AUC 6 ( PC ; n = 381 ) . Time to disease progression ( TTP ) was the primary end point . Secondary end points were overall survival time ( OS ) , response rate ( RR ) , safety , and tolerability . RESULTS With a median follow-up of 736 days ( range , 1 to 2,280 days ) , the median TTP was 13.2 and 13.5 months in the PC-PSC and PC groups , respectively ( P = .67 ) ; the median OS was 32 and 28.9 months , respectively ( P = .94 ) . The overall RR was higher in the PC group ( 41.5 % v 33.6 % ; P = .02 ) . Central and peripheral nervous system and GI toxicities were more common in the PC-PSC group . Ataxia occurred in 53.5 % and 3.2 % of PC-PSC- and PC-treated patients , respectively . Febrile neutropenia occurred more frequently in the PC-PSC group . More PC-PSC-treated patients discontinued therapy because of adverse events ( AEs ) , experienced serious AEs , and required paclitaxel dose reductions . CONCLUSION The addition of valspodar to PC did not improve TTP or OS and was more toxic compared with PC in untreated patients with advanced ovarian or primary peritoneal cancer 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 ] PURPOSE To determine the side effects and feasibility of cisplatin and carboplatin each in combination with paclitaxel as front-line therapy in advanced epithelial ovarian cancer . PATIENTS AND METHODS Patients were r and omly allocated to receive paclitaxel 175 mg/m(2 ) intravenously as a 3-hour infusion followed by either cisplatin 75 mg/m(2 ) or carboplatin ( area under the plasma concentration-time curve of 5 ) , both on day 1 . The schedule was repeated every 3 weeks for at least six cycles . Women allocated to paclitaxel-cisplatin were admitted to the hospital , whereas the carboplatin regimen was administered to out patients . RESULTS A total of 208 eligible patients were r and omized . Both regimens could be delivered in an optimal dose and without significant delay . Paclitaxel-carboplatin produced significantly less nausea and vomiting ( P : < .01 ) and less peripheral neurotoxicity ( P : = .04 ) but more granulocytopenia and thrombocytopenia ( P : < .01 ) . The overall response rate in 132 patients with measurable disease was 64 % ( 84 of 132 patients ) , and in patients with elevated CA 125 levels at start , it was 74 % ( 132 of 178 patients ) . With a median follow-up time of 37 months , the median progression-free survival time of all patients was 16 months and the median overall survival time was 31 months . The small number of patients entered onto the study caused wide confidence intervals ( CIs ) around the hazards ratio for progression-free survival of paclitaxel-carboplatin compared with paclitaxel-cisplatin ( hazards ratio , 1.07 ; 95 % CI , 0.78 to 1.48 ) and did not allow conclusions about efficacy . CONCLUSION Paclitaxel-carboplatin is a feasible regimen for out patients with ovarian cancer and has a better toxicity profile than paclitaxel-cisplatin PURPOSE To analyze the effect of different doses of paclitaxel with fixed doses of carboplatin in the treatment of ovarian cancer . PATIENTS AND METHODS Patients with histologically confirmed epithelial ovarian cancer , International Federation of Gynecology and Obstetrics stages IIB to IV , were eligible for this r and omized , multicenter study . Women were r and omly assigned to treatment with ( 1 ) carboplatin at the dose ( in milligrams ) corresponding to the following formula : target area under the free carboplatin plasma concentration versus 
    Output:
    
Survival of the control arm has frequently been underestimated in recent EOC RP3 trials .
Underestimating the outcome of the control arm may result in trials being underpowered to demonstrate the absolute benefit they were design ed to show