***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 Despite recent progress in the treatment of ovarian cancer , the majority of patients eventually relapse . There is little information on the effectiveness of chemotherapy in higher treatment lines . PATIENTS AND METHODS Characterization of the second to sixth line therapy and its effects on survival was carried out , based on data of n = 1620 patients from three large r and omized phase III trials investigating primary therapy . RESULTS Median progression-free survival ( PFS ) after the first , second , third , fourth and fifth relapse was 10.2 [ 95 % confidence interval ( CI ) 9.6 - 10.7 ] , 6.4 ( 5.9 - 7.0 ) , 5.6 ( 4.8 - 6.2 ) , 4.4 ( 3.7 - 4.9 ) and 4.1 ( 3.0 - 5.1 ) months , respectively . Median overall survival ( OS ) after the first , second , third , fourth and fifth relapse was 17.6 ( 95 % CI 16.4 - 18.6 ) , 11.3 ( 10.4 - 12.9 ) , 8.9 ( 7.8 - 9.9 ) , 6.2 ( 5.1 - 7.7 ) and 5.0 ( 3.8 - 10.4 ) months , respectively . The most frequent second and third line chemotherapy was platinum combination ( n = 313 , 24.5 % ) and topotecan ( n = 118 , 23.6 % ) , respectively . Relapse treatment improved PFS and OS at the second to fourth recurrence , although frequently not performed according to the st and ard of care . In multivariate analysis , platinum sensitivity and optimal primary tumor debulking were revealed as independent prognostic factors for PFS up to third relapse . CONCLUSION A maximum of three lines of subsequent relapse treatment seems to be beneficial for patients with recurrent ovarian cancer . Optimal primary tumor debulking and platinum sensitivity remain independent prognostic factors even after more frequent relapses 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 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 OBJECTIVE Because debate continues over the role of combination , platinum-based chemotherapy for platinum-sensitive ( PS ) , recurrent ovarian cancer ( OC ) , we compared overall survival ( OS ) , progression-free survival ( PFS ) , confirmed complete response rate and time to treatment failure in this population . METHODS Patients with recurrent stage III or IV OC , a progression-free and platinum-free interval of 6 - 24 months after first-line platinum-based chemotherapy and up to 12 courses of a non-platinum containing consolidation treatment were eligible . Patients were r and omized to i.v . pegylated liposomal doxorubicin ( PLD ) ( 30 mg/m2 ) plus i.v . carboplatin ( AUC=5 mg/mL min ) once every 4 weeks ( PLD arm ) or i.v . carboplatin alone ( AUC=5 mg/mL min ) once every 4 weeks . RESULTS The PLD arm enrolled 31 patients and the carboplatin alone arm 30 for a total of 61 patients out of 900 planned .  Response rates were 67 % for the PLD arm and 32 % for the carboplatin only arm ( Fisher 's exact p=0.02 ) . The estimated median PFS was 12 and 8 months for PLD versus carboplatin alone . The estimated median OS on the PLD arm was 26 months and 18 months on the carboplatin only arm ( p=0.02 ) . Twenty-six percent of the patients on the PLD arm reported grade 4 toxicities , all hematological in nature . CONCLUSION This study was closed early because of slow patient accrual . The response rate , median PFS and OS results are intriguing . These data suggest that there may be an advantage to the PLD plus carboplatin combination treatment in patients with PS , recurrent OC . The regimen should be further tested BACKGROUND The aim of this study was to determine whether the response rate for the paclitaxel-carboplatin combination is superior to carboplatin alone in the treatment of patients with platinum-sensitive recurrent ovarian carcinoma . PATIENTS AND METHODS Patients with recurrent ovarian carcinoma , 6 months after treatment with a platinum-based regimen and with no more than two previous chemotherapy lines , were r and omized to receive carboplatin area under the curve ( AUC ) 5 ( arm A ) or paclitaxel 175 mg/m(2 ) + carboplatin AUC 5 ( arm B ) . The primary end point was objective response , following a ' pick up the winner ' design . Secondary end points included time to progression ( TTP ) , overall survival , tolerability and quality of life ( QoL ) . RESULTS Eighty-one patients were r and omized and included in the intention-to-treat analysis . The response rate in arm B was 75.6 % [ 26.8 % complete response ( CR ) + 48.8 % partial response ( PR ) ] [ 95 % confidence interval ( CI ) 59.7 % to 87.6 % ] and 50 % in arm A ( 20 % CR + 30 % PR ) ( 95 % CI 33.8 % to 66.2 % ) . No significant differences were observed in grade 3 - 4 hematological toxicity . Conversely , mucositis , myalgia/arthralgia and peripheral neurophaty were more frequent in arm B. Median TTP was 49.1 weeks in arm B ( 95 % CI 36.9 - 61.3 ) and 33.7 weeks in arm A ( 95 % CI 25.8 - 41.5 ) . No significant differences were found in the QoL analysis . CONCLUSIONS Paclitaxel-carboplatin combination is a tolerable regimen with a higher response rate than carboplatin monotherapy in platinum-sensitive recurrent ovarian carcinoma Fifty-four patients with ovarian cancer who achieved a complete or partial remission with cisplatin or carboplatin  were rechallenged with the same drug or crossed over to the other platinum compound at relapse . Fifteen of 43 ( 35 % ) crossover patients and 1/11 ( 9 % ) rechallenged patients responded ; the difference was not significant and there was no difference in survival between the two groups . Responders survived significantly longer than nonresponders ( P = 0.001 ) but there was no survival difference between those who responded to a rechallenge and those who responded to crossing over to the other platinum compound . The progression-free interval between the end of initial treatment and relapse was a significant prognostic factor for response to treatment and survival ; 17 % ( 6/35 ) of patients who relapsed before 18 months responded as compared to 53 % ( 10/19 ) who relapsed after 18 months ( P = 0.006 ) and median survival was 221 and 486 days , respectively , for these two groups ( P = 0.026 ) OBJECTIVE The progression-free and median survival of patients with advanced ovarian cancer has not appreciably improved over the last decade . Novel targeted therapies , particularly antiangiogenic agents , may potentially improve clinical outcomes in patients with ovarian cancer . This phase II , open-label study evaluated oral pazopanib monotherapy in patients with low-volume recurrent ovarian cancer . METHODS Patients with recurrent epithelial ovarian , fallopian tube , or primary peritoneal carcinoma with complete CA-125 response to initial platinum-based chemotherapy and subsequent elevation of CA-125 to ≥ 42 U/mL ( > 2 × ULN ) were treated with pazopanib 800 mg once daily until PD or unacceptable toxicity . This Green-Dahlberg study required 2 CA-125 responses in stage I ( 20 patients ) to proceed to stage II ( 15 patients ) . The primary endpoint was CA-125 response ( ≥ 50 % decrease from baseline , confirmed ≥ 21 days after initial evaluation ) . RESULTS Eleven of 36 patients ( 31 % ) had a CA-125 response to pazopanib , with median time to response of 29 days and median response duration of 113 days . Overall response rate was 18 % in patients with measurable disease at baseline . The most common adverse events leading to discontinuation of study drug were grade 3 ALT ( 8 % ) and AST ( 8 % ) elevation . Only 1 grade 4 toxicity ( peripheral edema ) was reported . CONCLUSIONS Pazopanib monotherapy was relatively well tolerated , with toxicity similar to other small-molecule , oral angiogenesis inhibitors , and demonstrated promising single-agent activity in patients with recurrent ovarian cancer . Further studies evaluating the potential role of pazopanib in patients with o 
    Output:
    
In this individual patient data ( IPD ) meta- analysis , we have demonstrated that combination-platinum chemotherapy improves OS and PFS across all subgroups .
This provides the strongest evidence to date of the benefit of combination-platinum over single-agent platinum