***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 : Based on the efficacy of pegylated liposomal doxorubicin ( PLD ) in relapsed ovarian cancer , we are conducting a phase III study comparing carboplatin plus either paclitaxel or PLD as first-line therapy in advanced ovarian cancer . Because of limited phase I and II data on PLD plus carboplatin in this setting , we conducted an interim activity analysis . Patients and Methods : Patients with stage 1c-IV epithelial ovarian cancer were r and omized to carboplatin AUC 5 plus either paclitaxel 175 mg/m2 or PLD 30 mg/m2 every 3 weeks for 6 cycles . The interim activity analysis was planned according to a single-stage phase II design with an auspicated 50 % response rate ; 50 patients eligible for response assessment were required . Response was defined according to RECIST ( Response Evaluation Criteria in Solid Tumors ) . Results : A complete response was achieved in 14 patients ( 28 % ) and a partial response in 20 ( 40 % ) , which produced an overall response rate of 68 % . The activity exceeded the minimum required for study continuation . Stable disease was reported in an additional 10 patients ( 20 % ) . Conclusions : The adopted schedule of PLD plus carboplatin demonstrates activity as a first-line treatment for advanced ovarian cancer OBJECTIVE While primary cisplatin-based intraperitoneal chemotherapy has been shown to favorably impact survival in small-volume residual advanced ovarian cancer , there is a need to develop strategies that improve the effectiveness of this approach . METHODS A multi-center phase 2 trial was conducted that added intravenous pegylated liposomal doxorubicin ( day 8 ; 30 - 40 mg/m(2 ) ) to a regimen of intraperitoneal cisplatin ( day 2 ; 75 mg/m(2 ) ) and intravenous ( day 1 ; 135 mg/m(2 ) ) plus intraperitoneal ( day 8 ; 60 mg/m(2 ) ) paclitaxel . Treatment was initially delivered on an every 3-week schedule , but was modified to an every 4-week program due to excessive toxicity . Patients were to receive 6 cycles of this regimen . RESULTS Of 68 patients entering this trial , 63 patients were eligible and evaluable , of whom 39 ( 62 % ) completed 6 cycles . Overall , 32 ( 51 % ) experienced at least 1 grade 4 or worse toxicity ( most commonly hematologic ) including 5 treatment-related deaths . Median progression-free survival ( PFS ) was 25 months ( 2-year PFS : 52 % ) and median overall survival 51 months , an outcome similar to previous reports of cisplatin-based intraperitoneal chemotherapy in comparable patient population s. Seventeen patients ( 27 % of all eligible patients ) were without evidence of disease recurrence > 4 years following entry into the trial . CONCLUSION Both the overall trial outcome , and specifically the excessively severe systemic toxicity of this regimen would prevent its future development in this exact form . The provocative PFS in a subset of individuals should encourage the development of alternative strategies design ed to optimize the delivery of regional therapy in ovarian cancer management PURPOSE This r and omized , multicenter , phase III noninferiority trial was design ed to test the efficacy and safety of the combination of pegylated liposomal doxorubicin ( PLD ) with carboplatin ( CD ) compared with st and ard carboplatin and paclitaxel ( CP ) in patients with platinum-sensitive relapsed/recurrent ovarian cancer ( ROC ) . PATIENTS AND METHODS Patients with histologically proven ovarian cancer with recurrence more than 6 months after first- or second-line platinum and taxane-based therapies were r and omly assigned by stratified blocks to CD ( carboplatin area under the curve [ AUC ] 5 plus PLD 30 mg/m(2 ) ) every 4 weeks or CP ( carboplatin AUC 5 plus paclitaxel 175 mg/m(2 ) ) every 3 weeks for at least 6 cycles . Primary end point was progression-free survival ( PFS ) ; secondary end points were toxicity , quality of life , and overall survival . RESULTS Overall 976 patients were recruited . With median follow-up of 22 months , PFS for the CD arm was statistically superior to the CP arm ( hazard ratio , 0.821 ; 95 % CI , 0.72 to 0.94 ; P = .005 ) ; median PFS was 11.3 versus 9.4 months , respectively . Although overall survival data are immature for final analysis , we report here a total of 334 deaths . Overall severe nonhematologic toxicity ( 36.8 % v 28.4 % ; P < .01 ) leading to early discontinuation ( 15 % v 6 % ; P < .001 ) occurred more frequently in the CP arm . More frequent grade 2 or greater alopecia ( 83.6 % v 7 % ) , hypersensitivity reactions ( 18.8 % v 5.6 % ) , and sensory neuropathy ( 26.9 % v 4.9 % ) were observed in the CP arm ; more h and -foot syndrome ( grade 2 to 3 , 12.0 % v 2.2 % ) , nausea ( 35.2 % v 24.2 % ) , and mucositis ( grade 2 - 3 , 13.9 % v 7 % ) in the CD arm . CONCLUSION To our knowledge , this trial is the largest in recurrent ovarian cancer and has demonstrated superiority in PFS and better therapeutic index of CD over st and ard CP Background Platinum-based combinations are the st and ard second-line treatment for platinum-sensitive ovarian cancer ( OC ) . This r and omized phase II study was undertaken in order to compare the combination of carboplatin and pegylated liposomal doxorubicin ( LD ) with carboplatin and paclitaxel ( CP ) in this setting . Methods Patients with histologically confirmed recurrent OC , at the time of or more than 6 months after platinum-based chemotherapy , were r and omized to six cycles of  CP ( carboplatin AUC5 + paclitaxel 175 mg/m2 , d1q21 ) or CLD ( carboplatin AUC5 + pegylated LD 45 mg/m2 , d1q28 ) . Results A total of 189 eligible patients ( CP 96 , CLD 93 ) , with a median age of 63 years , median Performance Status ( PS ) 0 and a median platinum free interval ( PFI ) of 16.5 months , entered the study .  Discontinuation due to toxicity was higher in the CP patients ( 13.5 % versus 3 % , P = 0.016 ) . The overall response rate was similar : CP 58 % versus CLD 51 % , P = 0.309 ( Complete Response ; CR 34 % versus 23 % ) and there was no statistical difference in time-to-progression ( TTP ) or overall survival ( OS ; TTP 10.8 months CP versus 11.8 CLD , P = 0.904 ; OS 29.4 months CP versus 24.7 CLD , P = 0.454 ) . No toxic deaths were recorded . Neutropenia was the most commonly seen severe toxicity ( CP 30 % versus CLD 35 % ) . More frequent in CLD were severe thrombocytopenia ( 11 % versus 2 % , P = 0.016 ) , skin toxicity and Palmar-plantar erythrodysesthesia ( PPE ) grade 1 - 2 ( 38 % versus 9 % , P < 0.001 ) , while grade 3 neurotoxicity and alopecia were higher in CP ( 7 % versus 0 % , P = 0.029 , 20 % versus 5 % , P = 0.003 ) . PS and PFI were independent prognostic factors for TTP and OS . Conclusions The combination of pegylated LD with carboplatin is effective , showing less neurotoxicity and alopecia than paclitaxel-carboplatin . It thus warrants a further phase III evaluation as an alternative treatment option for platinum-sensitive OC patients .Trial Registration Australian New Zeal and Clinical Trials Registry : Background The MITO-2 ( Multicentre Italian Trials in Ovarian cancer ) study is a r and omized phase III trial comparing carboplatin plus paclitaxel to carboplatin plus pegylated liposomal doxorubicin in first-line chemotherapy of patients with ovarian cancer . Due to the paucity of published phase I data on the 3-weekly experimental schedule used , an early safety analysis was planned . Methods Patients with ovarian cancer ( stage Ic-IV ) , aged < 75 years , ECOG performance status ≤ 2 , were r and omized to carboplatin AUC 5 plus paclitaxel 175 mg/m2 , every 3 weeks or to carboplatin AUC 5 plus pegylated liposomal doxorubicin 30 mg/m2 , every 3 weeks . Treatment was planned for 6 cycles . Toxicity was coded according to the NCI-CTC version 2.0 . Results The pre-planned safety analysis was performed in July 2004 . Data from the first 50 patients treated with carboplatin plus pegylated liposomal doxorubicin were evaluated . Median age was 60 years ( range 34–75 ) . Forty-three patients ( 86 % ) completed 6 cycles . Two thirds of the patients had at least one cycle delayed due to toxicity , but 63 % of the cycles were administered on time . In most cases the reason for chemotherapy delay was neutropenia or other hematological toxicity . No delay due to palmar-plantar erythrodysesthesia ( PPE ) was recorded . No toxic death was recorded . Reported hematological toxicities were : grade ( G ) 3 anemia 16 % , G3/G4 neutropenia 36 % and 10 % respectively , G3/4 thrombocytopenia 22 % and 4 % respectively . Non-haematological toxicity was infrequent : pulmonary G1 6 % , heart rhythm G1 4 % , li 
    Output:
    
PLD/carbo is a reasonable alternative to PAC/carbo for the first-line treatment of EOC .
Although three-weekly PLD/carbo may be associated with increased dose delays and discontinuations compared with the st and ard PAC/carbo regimen , it might be more acceptable to women who wish to avoid alopecia or those at high risk of neurotoxicity .