human
***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: OBJECTIVE Intraperitoneal ( IP ) chemotherapy prolongs survival in optimally reduced ovarian cancer patients . For patients in whom optimal debulking can not be achieved , one could incorporate IP therapy post-operatively if the cancer was optimally debulked following neoadjuvant chemotherapy . We sought to evaluate overall survival ( OS ) , progression-free survival ( PFS ) , percent of patients optimally debulked and toxicity in patients treated with this strategy . METHODS Women with adenocarcinoma by biopsy or cytology with stage III/IV ( pleural effusions only ) epithelial ovarian , fallopian tube or primary peritoneal carcinoma that presented with bulky disease were treated with neoadjuvant intravenous ( IV ) paclitaxel 175 mg/m2 and carboplatin AUC 6 q 21 daysx3 cycles followed by surgery ( if > /=50 % decrease in CA125 ) . If optimally debulked they received IV paclitaxel 175 mg/m2 and IP carboplatin AUC 5 ( day 1 ) and IP paclitaxel 60 mg/m2 ( day 8) q 28 daysx6 cycles . RESULTS Sixty-two patients were registered . Four were ineligible . Fifty-six were evaluated for neoadjuvant chemotherapy toxicities . One patient died of pneumonia . Five patients had grade 4 toxicity , including neutropenia ( 3 ) , anemia , leukopenia , anorexia , fatigue , muscle weakness , respiratory infection , and cardiac ischemia . Thirty-six patients had debulking surgery . Two had grade 4 hemorrhage . Twenty-six patients received post-cytoreduction chemotherapy . Four had grade 4 neutropenia . At a median follow-up of 21 months , median PFS is 21 months and median OS is 32 months for all 58 patients . PFS and OS for the 26 patients who received IV/IP chemotherapy is 29 and 34 months respectively . CONCLUSIONS These results compare favorably with other studies of sub-optimally debulked patients BACKGROUND The primary analysis of the JGOG 3016 trial showed that a dose-dense paclitaxel and carboplatin regimen significantly improves progression-free and overall survival compared with the conventional regimen as first-line chemotherapy for patients with epithelial ovarian , fallopian tube , or primary peritoneal cancer . We report the long-term follow-up results for survival . METHODS This r and omised controlled trial was done at 85 centres in Japan . Patients with stage II-IV ovarian cancer were r and omly assigned to receive conventional treatment ( carboplatin area under the curve [ AUC ] 6 mg/mL per min and paclitaxel 180 mg/m(2 ) on day 1 ) or dose-dense treatment ( carboplatin AUC 6 mg/mL per min on day 1 and paclitaxel 80 mg/m(2 ) on days 1 , 8 , and 15 ) . The treatments were repeated every 3 weeks for six cycles ; responding patients had three additional cycles . The r and omisation was done central ly by telephone or fax , stratified by residual disease , stage , and histological type . The primary endpoint was progression-free survival ; overall survival was a secondary endpoint . Long-term information on adverse events was not collected . Efficacy analyses were by intention to treat . This study is registered with Clinical Trials.gov , number NCT00226915 . FINDINGS 637 patients were enrolled , of whom 631 were analysed ( 312 assigned to the dose-dense regimen , 319 to the conventional regimen ) . Median follow-up was 76·8 months ( IQR 68·9 - 85·6 ) . Median progression-free survival was significantly longer in the dose-dense treatment group than in the conventional treatment group ( 28·2 months [ 95 % CI 22·3 - 33·8 ] vs 17·5 months [ 15·7 - 21·7 ] ; hazard ratio [ HR ] 0·76 , 95 % CI 0·62 - 0·91 ; p=0·0037 ) . Median overall survival was 100·5 months ( 95 % CI 65·2-∞ ) in the dose-dense treatment group and 62·2 months ( 52·1 - 82·6 ) in the conventional treatment group ( HR 0·79 , 95 % CI 0·63 - 0·99 ; p=0·039 ) . INTERPRETATION Dose-dense treatment offers better survival  than conventional treatment and is a potential new st and ard of care for first-line chemotherapy for patients with advanced epithelial ovarian cancer BACKGROUND The international st and ard of care for women with suspected advanced ovarian cancer is surgical debulking followed by platinum-based chemotherapy . We aim ed to establish whether use of platinum-based primary chemotherapy followed by delayed surgery was an effective and safe alternative treatment regimen . METHODS In this phase 3 , non-inferiority , r and omised , controlled trial ( CHORUS ) undertaken in 87 hospitals in the UK and New Zeal and , we enrolled women with suspected stage III or IV ovarian cancer . We r and omly assigned women ( 1:1 ) either to undergo primary surgery followed by six cycles of chemotherapy , or to three cycles of primary chemotherapy , then surgery , followed by three more cycles of completion chemotherapy . Each 3-week cycle consisted of carboplatin AUC5 or AUC6 plus paclitaxel 175 mg/m(2 ) , or an alternative carboplatin combination regimen , or carboplatin monotherapy . We did the r and om assignment by use of a minimisation method with a r and om element , and stratified participants according to the r and omising centre , largest radiological tumour size , clinical stage , and prespecified chemotherapy regimen . Patients and investigators were not masked to group assignment . The primary outcome measure was overall survival . Primary analyses were done in the intention-to-treat population . To establish non-inferiority , the upper bound of a one-sided 90 % CI for the hazard ratio ( HR ) had to be less than 1.18 . This trial is registered , number IS RCT N74802813 , and is closed to new participants . FINDINGS Between March 1 , 2004 , and Aug 30 , 2010 , we r and omly assigned 552 women to treatment . Of the 550 women who were eligible , 276 were assigned to primary surgery and 274 to primary chemotherapy . All were included in the intention-to-treat analysis ; 251 assigned to primary surgery and 253 to primary chemotherapy were included in the per- protocol analysis . As of May 31 , 2014 , 451 deaths had occurred : 231 in the primary -surgery group versus 220 in the primary -chemotherapy group . Median overall survival was 22.6 months in the primary -surgery group versus 24.1 months in primary chemotherapy . The HR for death was 0.87 in favour of primary chemotherapy , with the upper bound of the one-sided 90 % CI 0.98 ( 95 % CI 0.72 - 1.05 ) . Grade 3 or 4 postoperative adverse events and deaths within 28 days after surgery were more common in the primary -surgery group than in the primary -chemotherapy group ( 60 [ 24 % ] of 252 women vs 30 [ 14 % ] of 209 , p=0.0007 , and 14 women [ 6 % ] vs 1 woman [ < 1 % ] , p=0.001 ) . The most common grade 3 or 4 postoperative adverse event was haemorrhage in both groups ( 8 women [ 3 % ] in the primary -surgery group vs 14 [ 6 % ] in the primary -chemotherapy group ) . 110 ( 49 % ) of 225 women receiving primary surgery and 102 ( 40 % ) of 253 receiving primary chemotherapy had a grade 3 or 4 chemotherapy related toxic effect ( p=0.0654 ) , mostly uncomplicated neutropenia ( 20 % and 16 % , respectively ) . One fatal toxic effect , neutropenic sepsis , occurred in the primary -chemotherapy group . INTERPRETATION In women with stage III or IV ovarian cancer , survival with primary chemotherapy is non-inferior to primary surgery . In this study population , giving primary chemotherapy before surgery is an acceptable st and ard of care for women with advanced ovarian cancer . FUNDING Cancer Research UK and the Royal College of Obstetricians and Gynaecologists PURPOSE To compare the efficacy and safety of pegylated liposomal doxorubicin ( PLD ) and topotecan in patients with epithelial ovarian carcinoma that recurred after or did n't respond to first-line , platinum-based chemotherapy . PATIENTS AND METHODS Patients with measurable and assessable disease were r and omized to receive either PLD 50 mg/m(2 ) as a 1-hour infusion every 4 weeks or topotecan 1.5 mg/m(2)/d for 5 consecutive days every 3 weeks . Patients were stratified prospect ively for platinum sensitivity and for the presence or absence of bulky disease . RESULTS A total of 474 patients were treated ( 239 PLD and 235 topotecan ) . They comprised the intent-to-treat population . The overall progression-free survival rates were similar between the two arms ( P = .095 ) . The overall response rates for PLD and topotecan were 19.7 % and 17.0 % , respectively ( P = .390 ) . Median overall survival times were 60 weeks for PLD and 56.7 weeks for topotecan . Data analyzed in platinum-sensitive patients demonstrated a statistically significant benefit from PLD for progression-free survival ( P = .037 ) , with medians of 28.9 for PLD versus 23.3 weeks for topotecan . For overall survival , PLD was significantly superior to topotecan ( P = .008 ) , with a median of 108 weeks versus 71.1 weeks . The platinum-refractory subgroup demonstrated a nonstatistically significant survival trend in favor of topotecan ( P = .455 ) . Severe hematologic toxicity was more common with topotecan and was more likely to be associated with dosage modification , or growth factor or blood product utilization . CONCLUSION The comparable efficacy , favorable safety profile , and convenient dosing support the role of PLD as a valuable treatment option in this patient population BACKGROUND Despite considerable improvement in the treatment of advanced ovarian cancer , the optimization of efficacy and tolerability remains an important issue . Therefore , we performed a r and omized , phase III non-inferiority trial comparing paclitaxel plus cisplatin ( PT ) with paclitaxel plus carboplatin ( TC ) in patients with advanced ovarian cancer . METHODS A total of 798 patients with International Federation of Gynecology and Obstetrics stage IIB-IV were r and omly assigned to receive six courses of either PT or TC at 3-week intervals . The primary endpoint was the proportion of patients without progression at 2 years . Secondary endpoints included toxicity , response to treatment , quality of life , and overall and progression-free survival time . Quality of life was evaluated using the European Organization for Research and Treatment of Cancer quality -of-life question naire (QLQ)-C30 , version 2.0 . Survival curves were calculated using the Kaplan-Meier method , and hazard ratios were estimated using the Cox proportional hazards model . RESULTS The proportion of patients without progression at 2 years was not statistically significantly different between the two treatment arms ( 40.0 % for PT versus 37.5 % for TC , difference = 2.5 % , one-sided 95 % confidence interval [ CI ] = - infinity to 8.2 % ) . Median progression-free survival time in the TC arm ( 17.2 months , 95 % CI = 15.2 to 19.3 months ) and the PT arm ( 19.1 months , 95 % CI = 16.7 to 21.5 months ) were also not statistically significantly different ; the same was true of median overall survival time ( 43.3 months , 95 % CI = 37.2 to 47.8 months versus 44.1 months , 95 % CI = 40.2 to 49.4 months , for the TC and PT arms , respectively ) . The TC regimen was associated with a higher frequency of hematologic toxicity , but a lower frequency of gastrointestinal and neurologic toxicity , than the PT regimen . Mean global quality -of-life scores at the end of treatment were statistically significantly better in the TC arm than in the PT arm ( 65.25 versus 51.97 , respectively ; difference = -13.28 , 95 % CI = -18.88 to -7.68 ) . CONCLUSION The TC regimen achieved comparable efficacy to the PT regimen but was associated with better tolerability and quality of life , and should , therefore , be considered as an important alternative for st and ard first-line chemotherapy in patients with advanced ovarian cancer OBJECTIVE The use of tumor debulking surgery in the management of epithel 
    Output:
    
agent
The published studies suggest that for selected women with stage IIIC or IV epithelial ovarian cancer , neoadjuvant chemotherapy and interval cytoreduction are non-inferior to primary cytoreduction and adjuvant chemotherapy with respect to overall and progression-free survival and are associated with less perioperative morbidity and mortality .
***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: OBJECTIVE Intraperitoneal ( IP ) chemotherapy prolongs survival in optimally reduced ovarian cancer patients . For patients in whom optimal debulking can not be achieved , one could incorporate IP therapy post-operatively if the cancer was optimally debulked following neoadjuvant chemotherapy . We sought to evaluate overall survival ( OS ) , progression-free survival ( PFS ) , percent of patients optimally debulked and toxicity in patients treated with this strategy . METHODS Women with adenocarcinoma by biopsy or cytology with stage III/IV ( pleural effusions only ) epithelial ovarian , fallopian tube or primary peritoneal carcinoma that presented with bulky disease were treated with neoadjuvant intravenous ( IV ) paclitaxel 175 mg/m2 and carboplatin AUC 6 q 21 daysx3 cycles followed by surgery ( if > /=50 % decrease in CA125 ) . If optimally debulked they received IV paclitaxel 175 mg/m2 and IP carboplatin AUC 5 ( day 1 ) and IP paclitaxel 60 mg/m2 ( day 8) q 28 daysx6 cycles . RESULTS Sixty-two patients were registered . Four were ineligible . Fifty-six were evaluated for neoadjuvant chemotherapy toxicities . One patient died of pneumonia . Five patients had grade 4 toxicity , including neutropenia ( 3 ) , anemia , leukopenia , anorexia , fatigue , muscle weakness , respiratory infection , and cardiac ischemia . Thirty-six patients had debulking surgery . Two had grade 4 hemorrhage . Twenty-six patients received post-cytoreduction chemotherapy . Four had grade 4 neutropenia . At a median follow-up of 21 months , median PFS is 21 months and median OS is 32 months for all 58 patients . PFS and OS for the 26 patients who received IV/IP chemotherapy is 29 and 34 months respectively . CONCLUSIONS These results compare favorably with other studies of sub-optimally debulked patients BACKGROUND The primary analysis of the JGOG 3016 trial showed that a dose-dense paclitaxel and carboplatin regimen significantly improves progression-free and overall survival compared with the conventional regimen as first-line chemotherapy for patients with epithelial ovarian , fallopian tube , or primary peritoneal cancer . We report the long-term follow-up results for survival . METHODS This r and omised controlled trial was done at 85 centres in Japan . Patients with stage II-IV ovarian cancer were r and omly assigned to receive conventional treatment ( carboplatin area under the curve [ AUC ] 6 mg/mL per min and paclitaxel 180 mg/m(2 ) on day 1 ) or dose-dense treatment ( carboplatin AUC 6 mg/mL per min on day 1 and paclitaxel 80 mg/m(2 ) on days 1 , 8 , and 15 ) . The treatments were repeated every 3 weeks for six cycles ; responding patients had three additional cycles . The r and omisation was done central ly by telephone or fax , stratified by residual disease , stage , and histological type . The primary endpoint was progression-free survival ; overall survival was a secondary endpoint . Long-term information on adverse events was not collected . Efficacy analyses were by intention to treat . This study is registered with Clinical Trials.gov , number NCT00226915 . FINDINGS 637 patients were enrolled , of whom 631 were analysed ( 312 assigned to the dose-dense regimen , 319 to the conventional regimen ) . Median follow-up was 76·8 months ( IQR 68·9 - 85·6 ) . Median progression-free survival was significantly longer in the dose-dense treatment group than in the conventional treatment group ( 28·2 months [ 95 % CI 22·3 - 33·8 ] vs 17·5 months [ 15·7 - 21·7 ] ; hazard ratio [ HR ] 0·76 , 95 % CI 0·62 - 0·91 ; p=0·0037 ) . Median overall survival was 100·5 months ( 95 % CI 65·2-∞ ) in the dose-dense treatment group and 62·2 months ( 52·1 - 82·6 ) in the conventional treatment group ( HR 0·79 , 95 % CI 0·63 - 0·99 ; p=0·039 ) . INTERPRETATION Dose-dense treatment offers better survival  than conventional treatment and is a potential new st and ard of care for first-line chemotherapy for patients with advanced epithelial ovarian cancer BACKGROUND The international st and ard of care for women with suspected advanced ovarian cancer is surgical debulking followed by platinum-based chemotherapy . We aim ed to establish whether use of platinum-based primary chemotherapy followed by delayed surgery was an effective and safe alternative treatment regimen . METHODS In this phase 3 , non-inferiority , r and omised , controlled trial ( CHORUS ) undertaken in 87 hospitals in the UK and New Zeal and , we enrolled women with suspected stage III or IV ovarian cancer . We r and omly assigned women ( 1:1 ) either to undergo primary surgery followed by six cycles of chemotherapy , or to three cycles of primary chemotherapy , then surgery , followed by three more cycles of completion chemotherapy . Each 3-week cycle consisted of carboplatin AUC5 or AUC6 plus paclitaxel 175 mg/m(2 ) , or an alternative carboplatin combination regimen , or carboplatin monotherapy . We did the r and om assignment by use of a minimisation method with a r and om element , and stratified participants according to the r and omising centre , largest radiological tumour size , clinical stage , and prespecified chemotherapy regimen . Patients and investigators were not masked to group assignment . The primary outcome measure was overall survival . Primary analyses were done in the intention-to-treat population . To establish non-inferiority , the upper bound of a one-sided 90 % CI for the hazard ratio ( HR ) had to be less than 1.18 . This trial is registered , number IS RCT N74802813 , and is closed to new participants . FINDINGS Between March 1 , 2004 , and Aug 30 , 2010 , we r and omly assigned 552 women to treatment . Of the 550 women who were eligible , 276 were assigned to primary surgery and 274 to primary chemotherapy . All were included in the intention-to-treat analysis ; 251 assigned to primary surgery and 253 to primary chemotherapy were included in the per- protocol analysis . As of May 31 , 2014 , 451 deaths had occurred : 231 in the primary -surgery group versus 220 in the primary -chemotherapy group . Median overall survival was 22.6 months in the primary -surgery group versus 24.1 months in primary chemotherapy . The HR for death was 0.87 in favour of primary chemotherapy , with the upper bound of the one-sided 90 % CI 0.98 ( 95 % CI 0.72 - 1.05 ) . Grade 3 or 4 postoperative adverse events and deaths within 28 days after surgery were more common in the primary -surgery group than in the primary -chemotherapy group ( 60 [ 24 % ] of 252 women vs 30 [ 14 % ] of 209 , p=0.0007 , and 14 women [ 6 % ] vs 1 woman [ < 1 % ] , p=0.001 ) . The most common grade 3 or 4 postoperative adverse event was haemorrhage in both groups ( 8 women [ 3 % ] in the primary -surgery group vs 14 [ 6 % ] in the primary -chemotherapy group ) . 110 ( 49 % ) of 225 women receiving primary surgery and 102 ( 40 % ) of 253 receiving primary chemotherapy had a grade 3 or 4 chemotherapy related toxic effect ( p=0.0654 ) , mostly uncomplicated neutropenia ( 20 % and 16 % , respectively ) . One fatal toxic effect , neutropenic sepsis , occurred in the primary -chemotherapy group . INTERPRETATION In women with stage III or IV ovarian cancer , survival with primary chemotherapy is non-inferior to primary surgery . In this study population , giving primary chemotherapy before surgery is an acceptable st and ard of care for women with advanced ovarian cancer . FUNDING Cancer Research UK and the Royal College of Obstetricians and Gynaecologists PURPOSE To compare the efficacy and safety of pegylated liposomal doxorubicin ( PLD ) and topotecan in patients with epithelial ovarian carcinoma that recurred after or did n't respond to first-line , platinum-based chemotherapy . PATIENTS AND METHODS Patients with measurable and assessable disease were r and omized to receive either PLD 50 mg/m(2 ) as a 1-hour infusion every 4 weeks or topotecan 1.5 mg/m(2)/d for 5 consecutive days every 3 weeks . Patients were stratified prospect ively for platinum sensitivity and for the presence or absence of bulky disease . RESULTS A total of 474 patients were treated ( 239 PLD and 235 topotecan ) . They comprised the intent-to-treat population . The overall progression-free survival rates were similar between the two arms ( P = .095 ) . The overall response rates for PLD and topotecan were 19.7 % and 17.0 % , respectively ( P = .390 ) . Median overall survival times were 60 weeks for PLD and 56.7 weeks for topotecan . Data analyzed in platinum-sensitive patients demonstrated a statistically significant benefit from PLD for progression-free survival ( P = .037 ) , with medians of 28.9 for PLD versus 23.3 weeks for topotecan . For overall survival , PLD was significantly superior to topotecan ( P = .008 ) , with a median of 108 weeks versus 71.1 weeks . The platinum-refractory subgroup demonstrated a nonstatistically significant survival trend in favor of topotecan ( P = .455 ) . Severe hematologic toxicity was more common with topotecan and was more likely to be associated with dosage modification , or growth factor or blood product utilization . CONCLUSION The comparable efficacy , favorable safety profile , and convenient dosing support the role of PLD as a valuable treatment option in this patient population BACKGROUND Despite considerable improvement in the treatment of advanced ovarian cancer , the optimization of efficacy and tolerability remains an important issue . Therefore , we performed a r and omized , phase III non-inferiority trial comparing paclitaxel plus cisplatin ( PT ) with paclitaxel plus carboplatin ( TC ) in patients with advanced ovarian cancer . METHODS A total of 798 patients with International Federation of Gynecology and Obstetrics stage IIB-IV were r and omly assigned to receive six courses of either PT or TC at 3-week intervals . The primary endpoint was the proportion of patients without progression at 2 years . Secondary endpoints included toxicity , response to treatment , quality of life , and overall and progression-free survival time . Quality of life was evaluated using the European Organization for Research and Treatment of Cancer quality -of-life question naire (QLQ)-C30 , version 2.0 . Survival curves were calculated using the Kaplan-Meier method , and hazard ratios were estimated using the Cox proportional hazards model . RESULTS The proportion of patients without progression at 2 years was not statistically significantly different between the two treatment arms ( 40.0 % for PT versus 37.5 % for TC , difference = 2.5 % , one-sided 95 % confidence interval [ CI ] = - infinity to 8.2 % ) . Median progression-free survival time in the TC arm ( 17.2 months , 95 % CI = 15.2 to 19.3 months ) and the PT arm ( 19.1 months , 95 % CI = 16.7 to 21.5 months ) were also not statistically significantly different ; the same was true of median overall survival time ( 43.3 months , 95 % CI = 37.2 to 47.8 months versus 44.1 months , 95 % CI = 40.2 to 49.4 months , for the TC and PT arms , respectively ) . The TC regimen was associated with a higher frequency of hematologic toxicity , but a lower frequency of gastrointestinal and neurologic toxicity , than the PT regimen . Mean global quality -of-life scores at the end of treatment were statistically significantly better in the TC arm than in the PT arm ( 65.25 versus 51.97 , respectively ; difference = -13.28 , 95 % CI = -18.88 to -7.68 ) . CONCLUSION The TC regimen achieved comparable efficacy to the PT regimen but was associated with better tolerability and quality of life , and should , therefore , be considered as an important alternative for st and ard first-line chemotherapy in patients with advanced ovarian cancer OBJECTIVE The use of tumor debulking surgery in the management of epithel 
    Output:
    