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: PURPOSE To determine if circadian timed ( CT ) chemotherapy results in improved response , progression-free survival ( PFS ) , overall survival ( OS ) , and lower toxicity , when compared with st and ard timed ( ST ) chemotherapy . MATERIAL S AND METHODS Eligibility criteria were stage III , IV , or recurrent endometrial cancer with poor potential for cure by radiation therapy or surgery ; measurable disease ; and no prior chemotherapy . Therapy was r and omized to schedules of ST doxorubicin 60 mg/m2 plus cisplatin 60 mg/m2 , or CT doxorubicin 60 mg/m2 at 6:00 am plus cisplatin 60 mg/m2 at 6:00 pm . Cycles were repeated every 3 weeks to a maximum of eight cycles . RESULTS The ST arm included 169 patients , and the CT arm included 173 patients . The objective response rate ( complete responses plus partial responses ) was 46 % in the ST group compared with 49 % in the CT group ( P = .26 , one tail ) . Median PFS and OS were 6.5 and 11.2 months , respectively , in the ST group ; and 5.9 and 13.2 months , respectively , in the CT group ( PFS : P = .31 ; OS : P = .21 , one tail ) . Median total doses were 209 mg/m2 doxorubicin and 349 mg/m2 cisplatin in the ST group , versus 246 mg/m2 doxorubicin and 354 mg/m2 cisplatin in the CT group . Grade 3 or 4 leukopenia occurred in 73 % of patients in the ST arm and in 63 % of patients in the CT arm . There were eight treatment-related deaths . CONCLUSION In this trial , no significant benefit in terms of response rate , PFS or OS , or toxicity profile was observed with CT doxorubicin plus cisplatin in patients with advanced or recurrent endometrial carcinoma Purpose The management of high-risk endometrial cancer ( HREC ) remains controversial . We conducted a prospect i ve multicenter phase-II clinical trial to evaluate an adjuvant chemotherapy ( CT ) with sequential radiotherapy ( RT ) in patients with HREC . Methods Patients with HREC from 8 institutions in Germany were enrolled . After surgery , patients received four cycles of paclitaxel 175 mg/m² ( P ) and carboplatin AUC5 ( C ) ( d1 , q21d ) and subsequent external pelvic radiation therapy ( 1.8 Gy/d , d1 - 5 ) at a total dose of 45 Gy with vaginal brachytherapy ( 3 × 5 Gy  ) . Quality of life ( QoL ) was assessed using the EORTC-QLQ-C30 question naire . Primary endpoints were tolerability , toxicity and QoL. Progression-free survival ( PFS ) was defined as secondary endpoint . Results Thirty-five patients were enrolled from 2004 through 2008 . Median follow-up was 24 months ( range 3–24 months ) . All patients received 4 cycles of P and C and completed RT . Overall , grade 3/4 haematological toxicity was 25.6 % . Three cycles were delayed because of leukopenia . Grade 3/4 non-haematologic toxicities were rare ( ≤3 % ) . No overall change in QoL occurred during treatment . Two-year median PFS and OS rates were both 75.8 % . Conclusions Adjuvant combination CT with P + C and sequential RT is well tolerated and a feasible regimen in patients with HREC . Subsequent phase-III trials are warranted BACKGROUND The purpose of this study is to assess the efficacy and safety of treatment with taxane plus platinum in combination therapies for advanced or recurrent endometrial carcinoma . PATIENTS AND METHODS Patients with measurable disease derived from histologically confirmed stage III/IV or recurrent endometrial carcinoma were r and omly assigned to receive docetaxel plus cisplatin ( DP ) , docetaxel plus carboplatin ( DC ) , or paclitaxel plus carboplatin ( TC ) every 3 weeks until disease progression or adverse events prohibited further therapy . Among these regimens , the study evaluated the tumor response rate as the primary end point as well as toxicity . RESULTS Ninety patients were enrolled . Of them , 88 were eligible and consequently 29 , 29 , and 30 patients were r and omly assigned to DP , DC , and TC , respectively . Tumor response rates were 51.7 % , 48.3 % , and 60.0 % in DP , DC , and TC , respectively ( P = 0.65 ) . The following toxic effects were observed : grade 3/4 neutropenia in 83.3 % , 90.0 % , and 76.6 % ; febrile neutropenia in 10.0 % , 6.7 % , and 3.3 % ; grade 3/4 thrombocytopenia in 6.7 % , 10.0 % , and 10.0 % ; grade 3/4 diarrhea in 13.3 % , 3.3 % , and 0 % , respectively ; and grade 3 neurotoxicity in 10.0 % of TC . These toxicity profiles were not significantly different . CONCLUSION The taxane plus platinum combination therapies could be c and i date s in further phase III trials for endometrial carcinoma BACKGROUND Combination chemotherapy yields better response rates which do not always lead to a survival advantage . The aim of this study was to investigate whether the reported differences in the efficacy and toxicity of monotherapy with doxorubicin ( DOX ) versus combination therapy with cisplatin ( CDDP ) in endometrial adenocarcinoma lead to significant advantage in favour of the combination . PATIENTS AND METHODS Eligible patients had histologically-proven advanced and /or recurrent endometrial adenocarcinoma and were chemo-naïve . Treatment consisted of either DOX 60 mg/m(2 ) alone or CDDP 50 mg/m2 added to DOX 60 mg/m2 , every 4 weeks . RESULTS A total of 177 patients were entered and median follow-up is 7.1 years . The combination DOX-CDDP was more toxic than DOX alone . Haematological toxicity consisted mainly of white blood cell toxicity grade 3 and 4 ( 55 % versus 30 % ) . Non-haematological toxicity consisted mainly of grade 3 and 4 alopecia ( 72 % versus 65 % ) and nausea/vomiting ( 36 % versus 12 % ) . The combination DOX-CDDP provided a significantly higher response rate than single agent DOX ( P < 0.001 ) . Thirty-nine patients ( 43 % ) responded on DOX-CDDP [ 13 complete responses ( CRs ) and 26 partial responses ( PRs ) ] , versus 15 patients ( 17 % ) on DOX alone ( 8 CR and 7 PR ) . The median overall survival ( OS ) was 9 months in the DOX-CDDP arm versus 7 months in the DOX alone arm ( Wilcoxon P = 0.0654 ) . Regression analysis showed that WHO performance status was statistically significant as a prognostic factor for survival , and stratifying for this factor , treatment effect reaches significance ( hazard ratio = 1.46 , 95 % confidence interval 1.05 - 2.03 , P = 0.024 ) . CONCLUSIONS In comparison to single agent DOX , the combination of DOX-CDDP results in higher but acceptable toxicity . The response rate produced is significantly higher , and a modest survival benefit is achieved with this combination regimen , especially in patients with a good performance status PURPOSE After initial surgery , there has been no established consensus regarding adjunctive therapy for patients with uterine carcinosarcoma ( CS ) . This study was design ed to compare patient outcome following treatment with adjuvant whole abdominal irradiation ( WAI ) versus ( vs. ) chemotherapy for patients with this rare group of female pelvic malignancies . PATIENTS AND METHODS Eligible , consenting women with stage I-IV uterine CS , no more than 1 cm postsurgical residuum and /or no extra-abdominal spread had their treatments r and omly assigned as either WAI or three cycles of cisplatin ( C ) , ifosfamide ( I ) , and mesna ( M ) . RESULTS 232 patients were enrolled , of whom 206 ( WAI=105 ; CIM=101 ) were deemed eligible . Patient demographics and characteristics were similar between arms . FIGO stage ( both arms ) was : I=64 ( 31 % ) ; II=26 ( 13 % ) ; III=92 ( 45 % ) ; IV=24 ( 12 % ) . The estimated crude probability of recurring within 5 years was 58 % ( WAI ) and 52 % ( CIM ) . Adjusting for stage and age , the recurrence rate was 21 % lower for CIM patients than for WAI patients ( relative hazard [RH]=0.789 , 95 % confidence interval [ CI ] : ( 0.530 - 1.176 ) , p=0.245 , 2-tail test ) . The estimated death rate was 29 % lower among the CIM group ( RH=0.712 , 95 % CI : 0.484 - 1.048 , p=0.085 , two-tail test ) . CONCLUSION We did not find a statistically significant advantage in recurrence rate or survival for adjuvant CIM over WAI in patients with uterine CS . However , the observed differences favor the use of combination chemotherapy in future trials Objective To prospect ively compare quality of life ( QOL ) outcomes in patients with advanced endometrial cancer treated with whole abdominal irradiation ( WAI ) or doxorubicin-cisplatin ( AP ) chemotherapy .  Methods Using the Fatigue Scale ( FS ) , Assessment of Peripheral Neuropathy ( APN ) , Functional Alterations due to Changes in Elimination ( FACE ) , and Functional Assessment of Cancer Therapy-General ( FACT-G ) , QOL was measured at : pre-treatment , end of treatment ( EOT ) , and 3 and 6 months post-treatment . Results 317 of 396 eligible patients provided a baseline QOL assessment .  The AP arm produced a statistically significant survival benefit along with greater toxicities , including peripheral neuropathy persisting up to 6 months . WAI patients reported worse FS ( p<0.001 ) and FACE ( p<0.001 ) scores at EOT and poorer FACE scores 3 months post-treatment ( p = 0.004 ) compared to AP patients . APN scores were significantly worse among AP patients at EOT , and 3 and 6 months post-treatment ( p<0.001 for all ) . There is no indication that FACT-G scores differed between the two arms at any assessment point . Conclusions The trade-off for increased survival with AP is its potential for clinical ly significant peripheral neuropathy . This should be discussed with patients , particularly those who work with their h and s or on their feet , in weighing therapeutic choices . Further research is needed to manage side effects having an enduring impact on QOL PURPOSE To determine whether the addition of paclitaxel to doxorubicin plus cisplatin improves overall survival ( OS ) in women with advanced or recurrent endometrial carcinoma . Secondary comparisons included progression-free survival ( PFS ) , response rate ( RR ) , and toxicities . PATIENTS AND METHODS Eligible , consenting patients received doxorubicin 60 mg/m(2 ) and cisplatin 50 mg/m(2 ) ( AP ) , or doxorubicin 45 mg/m(2 ) and cisplatin 50 mg/m(2 ) ( day 1 ) , followed by paclitaxel 160 mg/m(2 ) ( day 2 ) with filgrastim support ( TAP ) . The initial doxorubicin dose in the AP arm was reduced to 45 mg/m(2 ) in patients with prior pelvic radiotherapy and those older than 65 years . Both regimens were repeated every 3 weeks to a maximum of seven cycles . Patients completed a neurotoxicity question naire before each cycle . RESULTS Two hundred seventy-three women ( 10 ineligible ) were registered .  Objective response ( 57 % v 34 % ; P < .01 ) , PFS ( median , 8.3 v 5.3 months ; P < .01 ) , and OS ( median , 15.3 v 12.3 months ; P = .037 ) were improved with TAP . Treatment was hematologically well tolerated , with only 2 % of patients receiving AP , and 3 % of patients receiving TAP experiencing neutropenic fever . Neurologic toxicity was worse for those receiving TAP , with 12 % grade 3 , and 27 % grade 2 peripheral neuropathy , compared with 1 % and 4 % , respectively , in those receiving AP .  Patient-reported neurotoxicity was significantly higher in the TAP arm following two cycles of therapy . CONCLUSION TAP significantly improves RR , PFS , and OS compared with AP . Evaluation of this regimen in the high-risk adjuvant setting is warranted , but close attention should be paid to the increased risk of peripheral neuropathy O 
    Output:
    
agent
***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 To determine if circadian timed ( CT ) chemotherapy results in improved response , progression-free survival ( PFS ) , overall survival ( OS ) , and lower toxicity , when compared with st and ard timed ( ST ) chemotherapy . MATERIAL S AND METHODS Eligibility criteria were stage III , IV , or recurrent endometrial cancer with poor potential for cure by radiation therapy or surgery ; measurable disease ; and no prior chemotherapy . Therapy was r and omized to schedules of ST doxorubicin 60 mg/m2 plus cisplatin 60 mg/m2 , or CT doxorubicin 60 mg/m2 at 6:00 am plus cisplatin 60 mg/m2 at 6:00 pm . Cycles were repeated every 3 weeks to a maximum of eight cycles . RESULTS The ST arm included 169 patients , and the CT arm included 173 patients . The objective response rate ( complete responses plus partial responses ) was 46 % in the ST group compared with 49 % in the CT group ( P = .26 , one tail ) . Median PFS and OS were 6.5 and 11.2 months , respectively , in the ST group ; and 5.9 and 13.2 months , respectively , in the CT group ( PFS : P = .31 ; OS : P = .21 , one tail ) . Median total doses were 209 mg/m2 doxorubicin and 349 mg/m2 cisplatin in the ST group , versus 246 mg/m2 doxorubicin and 354 mg/m2 cisplatin in the CT group . Grade 3 or 4 leukopenia occurred in 73 % of patients in the ST arm and in 63 % of patients in the CT arm . There were eight treatment-related deaths . CONCLUSION In this trial , no significant benefit in terms of response rate , PFS or OS , or toxicity profile was observed with CT doxorubicin plus cisplatin in patients with advanced or recurrent endometrial carcinoma Purpose The management of high-risk endometrial cancer ( HREC ) remains controversial . We conducted a prospect i ve multicenter phase-II clinical trial to evaluate an adjuvant chemotherapy ( CT ) with sequential radiotherapy ( RT ) in patients with HREC . Methods Patients with HREC from 8 institutions in Germany were enrolled . After surgery , patients received four cycles of paclitaxel 175 mg/m² ( P ) and carboplatin AUC5 ( C ) ( d1 , q21d ) and subsequent external pelvic radiation therapy ( 1.8 Gy/d , d1 - 5 ) at a total dose of 45 Gy with vaginal brachytherapy ( 3 × 5 Gy  ) . Quality of life ( QoL ) was assessed using the EORTC-QLQ-C30 question naire . Primary endpoints were tolerability , toxicity and QoL. Progression-free survival ( PFS ) was defined as secondary endpoint . Results Thirty-five patients were enrolled from 2004 through 2008 . Median follow-up was 24 months ( range 3–24 months ) . All patients received 4 cycles of P and C and completed RT . Overall , grade 3/4 haematological toxicity was 25.6 % . Three cycles were delayed because of leukopenia . Grade 3/4 non-haematologic toxicities were rare ( ≤3 % ) . No overall change in QoL occurred during treatment . Two-year median PFS and OS rates were both 75.8 % . Conclusions Adjuvant combination CT with P + C and sequential RT is well tolerated and a feasible regimen in patients with HREC . Subsequent phase-III trials are warranted BACKGROUND The purpose of this study is to assess the efficacy and safety of treatment with taxane plus platinum in combination therapies for advanced or recurrent endometrial carcinoma . PATIENTS AND METHODS Patients with measurable disease derived from histologically confirmed stage III/IV or recurrent endometrial carcinoma were r and omly assigned to receive docetaxel plus cisplatin ( DP ) , docetaxel plus carboplatin ( DC ) , or paclitaxel plus carboplatin ( TC ) every 3 weeks until disease progression or adverse events prohibited further therapy . Among these regimens , the study evaluated the tumor response rate as the primary end point as well as toxicity . RESULTS Ninety patients were enrolled . Of them , 88 were eligible and consequently 29 , 29 , and 30 patients were r and omly assigned to DP , DC , and TC , respectively . Tumor response rates were 51.7 % , 48.3 % , and 60.0 % in DP , DC , and TC , respectively ( P = 0.65 ) . The following toxic effects were observed : grade 3/4 neutropenia in 83.3 % , 90.0 % , and 76.6 % ; febrile neutropenia in 10.0 % , 6.7 % , and 3.3 % ; grade 3/4 thrombocytopenia in 6.7 % , 10.0 % , and 10.0 % ; grade 3/4 diarrhea in 13.3 % , 3.3 % , and 0 % , respectively ; and grade 3 neurotoxicity in 10.0 % of TC . These toxicity profiles were not significantly different . CONCLUSION The taxane plus platinum combination therapies could be c and i date s in further phase III trials for endometrial carcinoma BACKGROUND Combination chemotherapy yields better response rates which do not always lead to a survival advantage . The aim of this study was to investigate whether the reported differences in the efficacy and toxicity of monotherapy with doxorubicin ( DOX ) versus combination therapy with cisplatin ( CDDP ) in endometrial adenocarcinoma lead to significant advantage in favour of the combination . PATIENTS AND METHODS Eligible patients had histologically-proven advanced and /or recurrent endometrial adenocarcinoma and were chemo-naïve . Treatment consisted of either DOX 60 mg/m(2 ) alone or CDDP 50 mg/m2 added to DOX 60 mg/m2 , every 4 weeks . RESULTS A total of 177 patients were entered and median follow-up is 7.1 years . The combination DOX-CDDP was more toxic than DOX alone . Haematological toxicity consisted mainly of white blood cell toxicity grade 3 and 4 ( 55 % versus 30 % ) . Non-haematological toxicity consisted mainly of grade 3 and 4 alopecia ( 72 % versus 65 % ) and nausea/vomiting ( 36 % versus 12 % ) . The combination DOX-CDDP provided a significantly higher response rate than single agent DOX ( P < 0.001 ) . Thirty-nine patients ( 43 % ) responded on DOX-CDDP [ 13 complete responses ( CRs ) and 26 partial responses ( PRs ) ] , versus 15 patients ( 17 % ) on DOX alone ( 8 CR and 7 PR ) . The median overall survival ( OS ) was 9 months in the DOX-CDDP arm versus 7 months in the DOX alone arm ( Wilcoxon P = 0.0654 ) . Regression analysis showed that WHO performance status was statistically significant as a prognostic factor for survival , and stratifying for this factor , treatment effect reaches significance ( hazard ratio = 1.46 , 95 % confidence interval 1.05 - 2.03 , P = 0.024 ) . CONCLUSIONS In comparison to single agent DOX , the combination of DOX-CDDP results in higher but acceptable toxicity . The response rate produced is significantly higher , and a modest survival benefit is achieved with this combination regimen , especially in patients with a good performance status PURPOSE After initial surgery , there has been no established consensus regarding adjunctive therapy for patients with uterine carcinosarcoma ( CS ) . This study was design ed to compare patient outcome following treatment with adjuvant whole abdominal irradiation ( WAI ) versus ( vs. ) chemotherapy for patients with this rare group of female pelvic malignancies . PATIENTS AND METHODS Eligible , consenting women with stage I-IV uterine CS , no more than 1 cm postsurgical residuum and /or no extra-abdominal spread had their treatments r and omly assigned as either WAI or three cycles of cisplatin ( C ) , ifosfamide ( I ) , and mesna ( M ) . RESULTS 232 patients were enrolled , of whom 206 ( WAI=105 ; CIM=101 ) were deemed eligible . Patient demographics and characteristics were similar between arms . FIGO stage ( both arms ) was : I=64 ( 31 % ) ; II=26 ( 13 % ) ; III=92 ( 45 % ) ; IV=24 ( 12 % ) . The estimated crude probability of recurring within 5 years was 58 % ( WAI ) and 52 % ( CIM ) . Adjusting for stage and age , the recurrence rate was 21 % lower for CIM patients than for WAI patients ( relative hazard [RH]=0.789 , 95 % confidence interval [ CI ] : ( 0.530 - 1.176 ) , p=0.245 , 2-tail test ) . The estimated death rate was 29 % lower among the CIM group ( RH=0.712 , 95 % CI : 0.484 - 1.048 , p=0.085 , two-tail test ) . CONCLUSION We did not find a statistically significant advantage in recurrence rate or survival for adjuvant CIM over WAI in patients with uterine CS . However , the observed differences favor the use of combination chemotherapy in future trials Objective To prospect ively compare quality of life ( QOL ) outcomes in patients with advanced endometrial cancer treated with whole abdominal irradiation ( WAI ) or doxorubicin-cisplatin ( AP ) chemotherapy .  Methods Using the Fatigue Scale ( FS ) , Assessment of Peripheral Neuropathy ( APN ) , Functional Alterations due to Changes in Elimination ( FACE ) , and Functional Assessment of Cancer Therapy-General ( FACT-G ) , QOL was measured at : pre-treatment , end of treatment ( EOT ) , and 3 and 6 months post-treatment . Results 317 of 396 eligible patients provided a baseline QOL assessment .  The AP arm produced a statistically significant survival benefit along with greater toxicities , including peripheral neuropathy persisting up to 6 months . WAI patients reported worse FS ( p<0.001 ) and FACE ( p<0.001 ) scores at EOT and poorer FACE scores 3 months post-treatment ( p = 0.004 ) compared to AP patients . APN scores were significantly worse among AP patients at EOT , and 3 and 6 months post-treatment ( p<0.001 for all ) . There is no indication that FACT-G scores differed between the two arms at any assessment point . Conclusions The trade-off for increased survival with AP is its potential for clinical ly significant peripheral neuropathy . This should be discussed with patients , particularly those who work with their h and s or on their feet , in weighing therapeutic choices . Further research is needed to manage side effects having an enduring impact on QOL PURPOSE To determine whether the addition of paclitaxel to doxorubicin plus cisplatin improves overall survival ( OS ) in women with advanced or recurrent endometrial carcinoma . Secondary comparisons included progression-free survival ( PFS ) , response rate ( RR ) , and toxicities . PATIENTS AND METHODS Eligible , consenting patients received doxorubicin 60 mg/m(2 ) and cisplatin 50 mg/m(2 ) ( AP ) , or doxorubicin 45 mg/m(2 ) and cisplatin 50 mg/m(2 ) ( day 1 ) , followed by paclitaxel 160 mg/m(2 ) ( day 2 ) with filgrastim support ( TAP ) . The initial doxorubicin dose in the AP arm was reduced to 45 mg/m(2 ) in patients with prior pelvic radiotherapy and those older than 65 years . Both regimens were repeated every 3 weeks to a maximum of seven cycles . Patients completed a neurotoxicity question naire before each cycle . RESULTS Two hundred seventy-three women ( 10 ineligible ) were registered .  Objective response ( 57 % v 34 % ; P < .01 ) , PFS ( median , 8.3 v 5.3 months ; P < .01 ) , and OS ( median , 15.3 v 12.3 months ; P = .037 ) were improved with TAP . Treatment was hematologically well tolerated , with only 2 % of patients receiving AP , and 3 % of patients receiving TAP experiencing neutropenic fever . Neurologic toxicity was worse for those receiving TAP , with 12 % grade 3 , and 27 % grade 2 peripheral neuropathy , compared with 1 % and 4 % , respectively , in those receiving AP .  Patient-reported neurotoxicity was significantly higher in the TAP arm following two cycles of therapy . CONCLUSION TAP significantly improves RR , PFS , and OS compared with AP . Evaluation of this regimen in the high-risk adjuvant setting is warranted , but close attention should be paid to the increased risk of peripheral neuropathy O 
    Output:
    