***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 In r and omized trials the combination of cisplatin and paclitaxel was superior to cisplatin and cyclophosphamide in advanced-stage epithelial ovarian cancer . Although in nonr and omized trials , carboplatin and paclitaxel was a less toxic and highly active combination regimen , there remained concern regarding its efficacy in patients with small-volume , resected , stage III disease . Thus , we conducted a noninferiority trial of cisplatin and paclitaxel versus carboplatin and paclitaxel in this population . PATIENTS AND METHODS Patients with advanced ovarian cancer and no residual mass greater than 1.0 cm after surgery were r and omly assigned to receive cisplatin 75 mg/m2 plus a 24-hour infusion of paclitaxel 135 mg/m2 ( arm I ) , or carboplatin area under the curve 7.5 intravenously plus paclitaxel 175 mg/m2 over 3 hours ( arm II ) . RESULTS Seven hundred ninety-two eligible patients were enrolled onto the study . Prognostic factors were similar in the two treatment groups . Gastrointestinal , renal , and metabolic toxicity , as well as grade 4 leukopenia , were significantly more frequent in arm I. Grade 2 or greater thrombocytopenia was more common in arm II . Neurologic toxicity was similar in both regimens . Median progression-free survival and overall survival were 19.4 and 48.7 months , respectively , for arm I compared with 20.7 and 57.4 months , respectively , for arm II . The relative risk ( RR ) of progression for the carboplatin plus paclitaxel group was 0.88 ( 95 % confidence interval [ CI ] , 0.75 to 1.03 ) and the RR of death was 0.84 ( 95 % CI , 0.70 to 1.02 ) . CONCLUSION In patients with advanced ovarian cancer , a chemotherapy regimen consisting of carboplatin plus paclitaxel results in less toxicity , is easier to administer , and is not inferior , when compared with cisplatin plus paclitaxel PURPOSE To determine whether continuing paclitaxel for an extended time period in women with advanced ovarian cancer who had achieved a clinical ly defined complete response to a platinum/paclitaxel-based chemotherapy  could prolong subsequent progression-free survival ( PFS ) and affect ultimate survival . PATIENTS AND METHODS Patients were r and omly assigned to either three or 12 cycles of single-agent paclitaxel administered every 28 days and were then followed up for progression-free and overall survival . RESULTS As of September 6 , 2001 , 277 patients ( 262 assessable ) had entered the trial , with a total of 54 PFS events having developed among 222 patients with follow-up data . With the exception of peripheral neuropathy , there were no major differences in toxicity between the regimens . The median PFS was 21 and 28 months in the three-cycle and 12-cycle paclitaxel arms , respectively . One-sided P values from an unadjusted log-rank test and an adjusted Cox model analysis ( for stratification factors ) were.0035 and .0023 , respectively , both in favor of the 12-cycle arm . The Cox model-adjusted three-cycle versus the 12-cycle progression hazard ratio was estimated to be 2.31 ( 99 % confidence interval , 1.08 to 4.94 ) . With a protocol -specified early termination boundary of P = .005 , these findings led the Southwest Oncology Group Data Safety Monitoring Committee to discontinue the trial . As of the date of study closure , there was no difference in overall survival between the treatment arms . CONCLUSION Twelve cycles of single-agent paclitaxel administered to women with advanced ovarian cancer who attain a clinical ly defined complete response to initial platinum/paclitaxel-based chemotherapy significantly prolongs the duration of PFS INTRODUCTION R and omized trials have demonstrated significant improvements in progression-free survival ( PFS ) with consolidation paclitaxel ( P ) and bevacizumab ( B )  following cytoreduction and adjuvant carboplatin/paclitaxel ( CP ) for advanced epithelial ovarian cancer ( EOC ) . We sought to evaluate the cost-effectiveness ( C/E ) of these consolidation strategies . METHODS A decision model was developed based on Gynecologic Oncology Group ( GOG ) protocol s # 178 and # 218 . Arm 1 is 6 cycles of CP . Arm 2 is 6 cycles of CP followed by 12 cycles of P ( CP+P ) . Arm 3 is 1 cycle of CP , 5 cycles of CPB , and 16 cycles of B ( CPB+B ) . Parameters include PFS , overall survival ( OS ) , cost , complications ( neuropathy for P and bowel perforation for B ) , and quality -of-life utility values . Sensitivity analyses were performed . RESULTS The incremental cost-effectiveness ratio ( ICER ) for CT+T is $ 13,402/ quality adjusted life year ( QALY ) gained compared to CP . For CPB+B compared to CP , the ICER is $ 326,530/QALY . When compared simultaneously , CPB+B is dominated , i.e. is more costly and less effective than CP+P. Results were robust to parameter variation . At a willingness to pay threshold of $ 100,000/QALY , CP+P was the preferred option throughout most of the decision space . Sensitivity analyses suggest that CPB+B would become the preferred option if it were to improve OS by 6.1 years over CP+P. CONCLUSIONS In this model , B consolidation for advanced EOC was associated with a modest improvement in effectiveness that is less than that with P consolidation and more costly . A statistically significant improvement in survival may improve the value of B consolidation PURPOSE To estimate the efficacy and toxicity of AMG 386 , an investigational peptide-Fc fusion protein that neutralizes the interaction between the Tie2 receptor and angiopoietin-1/2 , plus weekly paclitaxel in patients with recurrent ovarian cancer . PATIENTS AND METHODS Patients with recurrent epithelial ovarian , fallopian tube , or primary peritoneal cancer were r and omly assigned 1:1:1 to receive paclitaxel ( 80 mg/m(2 ) once weekly [ QW ] , 3 weeks on/1 week off ) plus intravenous AMG 386 10 mg/kg QW ( arm A ) , AMG 386 3 mg/kg QW ( arm B ) , or placebo QW ( arm C ) . The primary end point was progression-free survival ( PFS ) . Secondary end points included overall survival , objective response , CA-125 response , safety , and pharmacokinetics . RESULTS One hundred sixty-one patients were r and omly assigned . Median PFS was 7.2 months ( 95 % CI , 5.3 to 8.1 months ) in arm A , 5.7 months ( 95 % CI , 4.6 to 8.0 months ) in arm B , and 4.6 months ( 95 % CI , 1.9 to 6.7 months ) in arm C. The hazard ratio for arms A and B combined versus arm C was 0.76 ( 95 % CI , 0.52 to 1.12 ; P = .165 ) . Further analyses suggested an exploratory dose-response effect for PFS across arms ( Tarone 's test , P = .037 ) . Objective response rates for arms A , B , and C were 37 % , 19 % , and 27 % , respectively . The incidence of grade ≥ 3 adverse events ( AEs ) in arms A , B , and C was 65 % , 55 % , and 64 % , respectively . Frequent AEs included hypertension ( 8 % , 6 % , and 5 % in arms A , B , and C , respectively ) , peripheral edema ( 71 % , 51 % , and 22 % in arms A , B , and C , respectively ) , and hypokalemia ( 21 % , 15 % , and 5 % in arms A , B , and C , respectively ) . AMG 386 exhibited linear pharmacokinetic properties at the tested doses . CONCLUSION AMG 386 combined with weekly paclitaxel was tolerable , with a manageable and distinct toxicity profile . The data suggest evidence of antitumor activity and a dose-response effect , warranting further studies in ovarian cancer BACKGROUND Paclitaxel and carboplatin given every 3 weeks is st and ard treatment for advanced ovarian carcinoma . Attempts to improve patient survival by including other drugs have yielded disappointing results . We compared a conventional regimen of paclitaxel and carboplatin with a dose-dense weekly regimen in women with advanced ovarian cancer . METHODS Patients with stage II to IV epithelial ovarian cancer , fallopian tube cancer , or primary peritoneal cancer were eligible for enrolment in this phase 3 , open-label , r and omised controlled trial at 85 centres in Japan . Patients were r and omly assigned by computer-generated r and omisation sequence to receive six cycles of either paclitaxel ( 180 mg/m(2 ) ; 3-h intravenous infusion ) plus carboplatin ( area under the curve [ AUC ] 6 mg/mL per min ) , given on day 1 of a 21-day cycle ( conventional regimen ; n=320 ) , or dose-dense paclitaxel ( 80 mg/m(2 ) ; 1-h intravenous infusion ) given on days 1 , 8 , and 15 plus carboplatin given on day 1 of a 21-day cycle ( dose-dense regimen ; n=317 ) . The primary endpoint was progression-free survival . Analysis was by intention to treat ( ITT ) . This trial is registered with Clinical Trials.gov , number NCT00226915 . FINDINGS 631 of the 637 enrolled patients were eligible for treatment and were included in the ITT population ( dose-dense regimen , n=312 ; conventional regimen , n=319 ) . Median progression-free survival was longer in the dose-dense treatment group ( 28.0 months , 95 % CI 22.3 - 35.4 ) than in the conventional treatment group ( 17.2 months , 15.7 - 21.1 ; hazard ratio [ HR ] 0.71 ; 95 % CI 0.58 - 0.88 ; p=0.0015 ) . Overall survival at 3 years was higher in the dose-dense regimen group ( 72.1 % ) than in the conventional treatment group ( 65.1 % ; HR 0.75 , 0.57 - 0.98 ; p=0.03 ) . 165 patients assigned to the dose-dense regimen and 117 assigned to the conventional regimen discontinued treatment early . Reasons for participant dropout were balanced between the groups , apart from withdrawal because of toxicity , which was higher in the dose-dense regimen group than in the conventional regimen group ( n=113 vs n=69 ) . The most common adverse event was neutropenia ( dose-dense regimen , 286 [ 92 % ] of 312 ; conventional regimen , 276 [ 88 % ] of 314 ) . The frequency of grade 3 and 4 anaemia was higher in the dose-dense treatment group ( 214 [ 69 % ] ) than in the conventional treatment group ( 137 [ 44 % ] ; p<0.0001 ) . The frequencies of other toxic effects were similar between groups . INTERPRETATION Dose-dense weekly paclitaxel plus carboplatin improved survival compared with the conventional regimen and represents a new treatment option in women with advanced epithelial ovarian cancer . FUNDING Bristol-Myers Squibb PURPOSE Vascular endothelial growth factor ( VEGF ) seems to be a promoter of tumor progression for epithelial ovarian cancer ( EOC ) and primary peritoneal cancer ( PPC ) . We conducted a phase II trial to assess the efficacy and tolerability of single-agent bevacizumab , an anti-VEGF monoclonal antibody . PATIENTS AND METHODS Eligible patients had persistent or recurrent EOC/PPC after one to two prior cytotoxic regimens , measurable disease , and Gynecologic Oncology Group performance status of at least 2 . Treatment consisted of bevacizumab 15 mg/kg intravenously every 21 days until disease progression or prohibitive toxicity . Primary end points were progression-free survival ( PFS ) at 6 months and clinical response . RESULTS The study consisted of 62 eligible and assessable patients , median age 57 years , 41 ( 66.1 % ) having received two prior regimens and 36 ( 58.1 % ) [ CORRECTED ] considered platinum resistant . Grade 3 adverse events at least possibly related to bevacizumab were hematologic ( 1 ) , GI ( 3 ) , hypertension ( 6 ) , thromboembolism ( 1 ) , allergy ( 2 ) , hepatic ( 1 ) , pain ( 3 ) 
    Output:
    
The most common adverse events associated with bevacizumab  included hypertension , proteinuria and gastrointestinal perforation .
Conclusion The addition of bevacizumab to chemotherapy followed by bevacizumab significantly improved PFS and OS in frontline setting and PFS in recurrent setting s compared with that of chemotherapy alone in patients with advanced ovarian cancer