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 OBJECTIVES To evaluate outcome in patients with clinical stage I/II papillary serous ( PS ) or clear cell ( CC ) endometrial carcinoma treated with whole abdominal radiotherapy .  METHODS After total abdominal hysterectomy with bilateral salpingo-oophorectomy , pelvic/para-aortic lymph node sampling , and peritoneal washings , eligible patients received radiotherapy ( RT ) to the abdomen ( 3000 cGy at 150 cGy/day ) with a pelvic boost ( 1980 cGy at 180 cGy/day ) . RESULTS Among 21 PS patients ( median age : 68 years ) , one refused therapy , and another received a non- protocol vaginal boost . In total , eight patients died of disease ( DOD ) between 9.6 and 35.2 months . Five others died due to protocol treatment ( 1 ) , toxicity from subsequent chemotherapy ( 1 ) , intercurrent disease ( 1 ) , and unknown cause ( 2 ) . Five-year progression-free survival ( PFS ) was 38 % . Among treated patients who DOD , sites of recurrence included lung ( 2 ) , lung/vagina ( 1 ) , abdomen/pelvis ( 1 ) , vagina ( 1 ) , and abdomen ( 2 ) . Among 13 CC patients ( median age : 63 years ) , one received pelvic RT only and died with intercurrent disease . Five others died due to DOD ( 3 ) , intercurrent disease ( 1 ) , and unknown cause ( 1 ) . Five-year PFS was 54 % . Among patients who DOD , sites of recurrence included lung ( 1 ) , vagina ( 1 ) , and unknown ( 1 ) . Grade 3/4 toxicities for both histologic groups included gastrointestinal ( three grade 4 ; three grade 3 ) , hematologic ( one grade 4 ) , and cutaneous ( one grade 3 ) . CONCLUSIONS Over half of the treatment failures were within the radiation field . Systemic chemotherapy , radiosensitizing chemotherapy , or sequential radiation and chemotherapy should be considered in future adjuvant trials for these patients Adjuvant therapy of early-stage uterine papillary serous carcinoma ( UPSC ) and clear cell carcinoma ( CCC ) is controversial . We conducted a prospect i ve cohort study to evaluate outcomes of patients with early-stage UPSC or CCC who were followed without adjuvant therapy after complete surgical staging . From 2000 to 2006 , we evaluated all consecutive patients with stage IA/IB UPSC or CCC who had surgical staging by a gynecological oncologist at the London Health Sciences Centre , Canada . Follow-up consisted of history and physical examination every 3 months for 2 years , then every 6 months for the next 3 years . Primary outcome measure was 2-year disease-free survival . There were 22 evaluable patients . Mean patient age was 63.4 years . Median number of pelvic and para-aortic lymph nodes resected was 15 ( range 2–39 ) and 4 ( range 0–12 ) , respectively . Thirteen had UPSC , seven had CCC , and two had both UPSC and CCC . Nine had stage IA and 13 had stage IB disease . Median follow-up was 25 months ( range 6–72 ) . Only one patient has recurred ( stage IB UPSC , isolated vault recurrence 10 months after surgery ) , but she is well 9 months after receiving pelvic radiotherapy and vault brachytherapy .  Two-year disease-free survival was 95 % . These results suggest that adjuvant therapy may not be necessary for stage IA and IB UPSC and CCC after surgical staging . Further prospect i ve evaluation of different adjuvant therapy practice s is required for early-stage UPSC and CCC , which may be useful in the design of future clinical trials OBJECTIVE Our purpose was to assess the effect of adjuvant platinum-based , multiagent chemotherapy followed by conventional radiotherapy on the recurrence-free interval , patterns of recurrence , and survival of women with completely resected , poor-prognosis endometrial carcinoma . STUDY DESIGN Surgical stage IC and II endometrial carcinomas involving the outer one third of myometrium and completely resected stage III and IV carcinomas were eligible for six cycles of cisplatin ( Platinol ) , doxorubicin hydrochloride ( Adriamycin ) , and cyclophosphamide ( Cytoxan ) ( 50 , 50 , 500 mg/m2 ) , followed by external beam radiotherapy to pelvis , pelvis and periaortic chain , or whole abdomen , on the basis of documented disease . RESULTS Forty-seven women were registered between April 1 , 1984 , and Oct. 10 , 1992 ; 39 were eligible for review . Six were stage I , 28 were stage III , and five were stage IV . Two tumors were grade I , eight were grade 2 , and 29 were grade 3 . Twenty-three were endometrioid adenocarcinomas , eight papillary serous , six adenosquamous , and two clear cell . Thirty-seven patients ( 94.9 % ) completed six courses of chemotherapy , with no deaths ascribed to treatment . Grade 3 or 4 neutropenia was experienced by 17 ( 44 % ) and sepsis by three ( 8 % ) . Current median follow-up is 27.3 months . Fifteen patients ( 38.5 % ) have recurrence , and 14 have died after a median interval of 26.9 months . The 2-year progression-free interval is 72.5 % for nonpapillary serous histologic types and 22.5 % for papillary serous cancers ( p = 0.0074 ) . CONCLUSION Adjuvant chemotherapy with Platinol , Adriamycin , and Cytoxan followed by radiation therapy is well tolerated and seems to confer a survival advantage to women with nonpapillary serous endometrial carcinoma with a poor prognosis compared with historic controls treated by surgery or radiotherapy 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 PURPOSE Doxorubicin and cisplatin have activity in endometrial carcinoma and at initiation of this study ranked as the most active agents . This trial of stage III , IV , or recurrent disease evaluated whether combining these agents increases response rate ( RR ) and prolongs progression-free survival ( PFS ) and overall survival ( OS ) over doxorubicin alone . PATIENTS AND METHODS Of 299 patients registered , 281 ( 94 % ) were eligible . Regimens were doxorubicin 60 mg/m(2 ) intravenously or doxorubicin 60 mg/m(2 ) plus cisplatin 50 mg/m(2 ) every 3 weeks until disease progression , unacceptable toxicity , or a total of 500 mg/m(2 ) doxorubicin . RESULTS There were 12 ( 8 % ) complete ( CR ) and 26 ( 17 % ) partial responses ( PR ) among 150 patients receiving doxorubicin versus 25 ( 19 % ) CRs and 30 ( 23 % ) PRs among patients receiving the combination . The overall response rate was higher among patients receiving the combination ( 42 % ) compared with patients receiving doxorubicin ( 25 % ; P = .004 ) . Median PFS was 5.7 and 3.8 months , respectively , for the combination and single agent . The PFS hazard ratio was 0.736 ( 95 % CI , 0.577 to 0.939 ; P = .014 ) . Median OS was 9.0 and 9.2 months , respectively , for the combination and single agent . Overall death rates were similar in the two groups ( hazard ratio , 0.928 ; 95 % CI , 0.727 to 1.185 ) . Nausea , vomiting , and hematologic toxicities were common . The combination produced more grade 3 to 4 leukopenia ( 62 % v 40 % ) , thrombocytopenia ( 14 % v 2 % ) , anemia ( 22 % v 4 % ) , and nausea/vomiting ( 13 % v 3 % ) . CONCLUSION Adding cisplatin to doxorubicin in advanced endometrial carcinoma improves RR and PFS with a negligible impact on OS and produces increased toxicity . These results have served as a building block for subsequent phase III trials in patients with disseminated and high-risk limited endometrial carcinoma BACKGROUND This study was performed to determine whether 24-h paclitaxel plus doxorubicin and filgrastim was superior to cisplatin plus doxorubicin in patients with endometrial cancer with respect to response , progression-free survival ( PFS ) and overall survival ( OS ) . PATIENTS AND METHODS Eligible chemotherapy-naïve patients were r and omly assigned to doxorubicin 60 mg/m2 intravenously ( i.v . ) followed by cisplatin 50 mg/m2 i.v . ( arm 1 , n=157 ) or doxorubicin 50 mg/m2 i.v . followed 4 h later by paclitaxel 150 mg/m2 i.v . over 24 h plus filgrastim 5 microg/ 
    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 OBJECTIVES To evaluate outcome in patients with clinical stage I/II papillary serous ( PS ) or clear cell ( CC ) endometrial carcinoma treated with whole abdominal radiotherapy .  METHODS After total abdominal hysterectomy with bilateral salpingo-oophorectomy , pelvic/para-aortic lymph node sampling , and peritoneal washings , eligible patients received radiotherapy ( RT ) to the abdomen ( 3000 cGy at 150 cGy/day ) with a pelvic boost ( 1980 cGy at 180 cGy/day ) . RESULTS Among 21 PS patients ( median age : 68 years ) , one refused therapy , and another received a non- protocol vaginal boost . In total , eight patients died of disease ( DOD ) between 9.6 and 35.2 months . Five others died due to protocol treatment ( 1 ) , toxicity from subsequent chemotherapy ( 1 ) , intercurrent disease ( 1 ) , and unknown cause ( 2 ) . Five-year progression-free survival ( PFS ) was 38 % . Among treated patients who DOD , sites of recurrence included lung ( 2 ) , lung/vagina ( 1 ) , abdomen/pelvis ( 1 ) , vagina ( 1 ) , and abdomen ( 2 ) . Among 13 CC patients ( median age : 63 years ) , one received pelvic RT only and died with intercurrent disease . Five others died due to DOD ( 3 ) , intercurrent disease ( 1 ) , and unknown cause ( 1 ) . Five-year PFS was 54 % . Among patients who DOD , sites of recurrence included lung ( 1 ) , vagina ( 1 ) , and unknown ( 1 ) . Grade 3/4 toxicities for both histologic groups included gastrointestinal ( three grade 4 ; three grade 3 ) , hematologic ( one grade 4 ) , and cutaneous ( one grade 3 ) . CONCLUSIONS Over half of the treatment failures were within the radiation field . Systemic chemotherapy , radiosensitizing chemotherapy , or sequential radiation and chemotherapy should be considered in future adjuvant trials for these patients Adjuvant therapy of early-stage uterine papillary serous carcinoma ( UPSC ) and clear cell carcinoma ( CCC ) is controversial . We conducted a prospect i ve cohort study to evaluate outcomes of patients with early-stage UPSC or CCC who were followed without adjuvant therapy after complete surgical staging . From 2000 to 2006 , we evaluated all consecutive patients with stage IA/IB UPSC or CCC who had surgical staging by a gynecological oncologist at the London Health Sciences Centre , Canada . Follow-up consisted of history and physical examination every 3 months for 2 years , then every 6 months for the next 3 years . Primary outcome measure was 2-year disease-free survival . There were 22 evaluable patients . Mean patient age was 63.4 years . Median number of pelvic and para-aortic lymph nodes resected was 15 ( range 2–39 ) and 4 ( range 0–12 ) , respectively . Thirteen had UPSC , seven had CCC , and two had both UPSC and CCC . Nine had stage IA and 13 had stage IB disease . Median follow-up was 25 months ( range 6–72 ) . Only one patient has recurred ( stage IB UPSC , isolated vault recurrence 10 months after surgery ) , but she is well 9 months after receiving pelvic radiotherapy and vault brachytherapy .  Two-year disease-free survival was 95 % . These results suggest that adjuvant therapy may not be necessary for stage IA and IB UPSC and CCC after surgical staging . Further prospect i ve evaluation of different adjuvant therapy practice s is required for early-stage UPSC and CCC , which may be useful in the design of future clinical trials OBJECTIVE Our purpose was to assess the effect of adjuvant platinum-based , multiagent chemotherapy followed by conventional radiotherapy on the recurrence-free interval , patterns of recurrence , and survival of women with completely resected , poor-prognosis endometrial carcinoma . STUDY DESIGN Surgical stage IC and II endometrial carcinomas involving the outer one third of myometrium and completely resected stage III and IV carcinomas were eligible for six cycles of cisplatin ( Platinol ) , doxorubicin hydrochloride ( Adriamycin ) , and cyclophosphamide ( Cytoxan ) ( 50 , 50 , 500 mg/m2 ) , followed by external beam radiotherapy to pelvis , pelvis and periaortic chain , or whole abdomen , on the basis of documented disease . RESULTS Forty-seven women were registered between April 1 , 1984 , and Oct. 10 , 1992 ; 39 were eligible for review . Six were stage I , 28 were stage III , and five were stage IV . Two tumors were grade I , eight were grade 2 , and 29 were grade 3 . Twenty-three were endometrioid adenocarcinomas , eight papillary serous , six adenosquamous , and two clear cell . Thirty-seven patients ( 94.9 % ) completed six courses of chemotherapy , with no deaths ascribed to treatment . Grade 3 or 4 neutropenia was experienced by 17 ( 44 % ) and sepsis by three ( 8 % ) . Current median follow-up is 27.3 months . Fifteen patients ( 38.5 % ) have recurrence , and 14 have died after a median interval of 26.9 months . The 2-year progression-free interval is 72.5 % for nonpapillary serous histologic types and 22.5 % for papillary serous cancers ( p = 0.0074 ) . CONCLUSION Adjuvant chemotherapy with Platinol , Adriamycin , and Cytoxan followed by radiation therapy is well tolerated and seems to confer a survival advantage to women with nonpapillary serous endometrial carcinoma with a poor prognosis compared with historic controls treated by surgery or radiotherapy 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 PURPOSE Doxorubicin and cisplatin have activity in endometrial carcinoma and at initiation of this study ranked as the most active agents . This trial of stage III , IV , or recurrent disease evaluated whether combining these agents increases response rate ( RR ) and prolongs progression-free survival ( PFS ) and overall survival ( OS ) over doxorubicin alone . PATIENTS AND METHODS Of 299 patients registered , 281 ( 94 % ) were eligible . Regimens were doxorubicin 60 mg/m(2 ) intravenously or doxorubicin 60 mg/m(2 ) plus cisplatin 50 mg/m(2 ) every 3 weeks until disease progression , unacceptable toxicity , or a total of 500 mg/m(2 ) doxorubicin . RESULTS There were 12 ( 8 % ) complete ( CR ) and 26 ( 17 % ) partial responses ( PR ) among 150 patients receiving doxorubicin versus 25 ( 19 % ) CRs and 30 ( 23 % ) PRs among patients receiving the combination . The overall response rate was higher among patients receiving the combination ( 42 % ) compared with patients receiving doxorubicin ( 25 % ; P = .004 ) . Median PFS was 5.7 and 3.8 months , respectively , for the combination and single agent . The PFS hazard ratio was 0.736 ( 95 % CI , 0.577 to 0.939 ; P = .014 ) . Median OS was 9.0 and 9.2 months , respectively , for the combination and single agent . Overall death rates were similar in the two groups ( hazard ratio , 0.928 ; 95 % CI , 0.727 to 1.185 ) . Nausea , vomiting , and hematologic toxicities were common . The combination produced more grade 3 to 4 leukopenia ( 62 % v 40 % ) , thrombocytopenia ( 14 % v 2 % ) , anemia ( 22 % v 4 % ) , and nausea/vomiting ( 13 % v 3 % ) . CONCLUSION Adding cisplatin to doxorubicin in advanced endometrial carcinoma improves RR and PFS with a negligible impact on OS and produces increased toxicity . These results have served as a building block for subsequent phase III trials in patients with disseminated and high-risk limited endometrial carcinoma BACKGROUND This study was performed to determine whether 24-h paclitaxel plus doxorubicin and filgrastim was superior to cisplatin plus doxorubicin in patients with endometrial cancer with respect to response , progression-free survival ( PFS ) and overall survival ( OS ) . PATIENTS AND METHODS Eligible chemotherapy-naïve patients were r and omly assigned to doxorubicin 60 mg/m2 intravenously ( i.v . ) followed by cisplatin 50 mg/m2 i.v . ( arm 1 , n=157 ) or doxorubicin 50 mg/m2 i.v . followed 4 h later by paclitaxel 150 mg/m2 i.v . over 24 h plus filgrastim 5 microg/ 
    Output:
    