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: Both single-agent cisplatin and the combination of doxorubicin and cyclophosphamide demonstrated moderate activity against endometrial carcinoma in earlier salvage trials . Since January 1979 , 102 patients with advanced primary ( n = 42 ) or recurrent ( n = 60 ) endometrial carcinoma were prospect ively treated with cisplatin ( 50 mg/m2 ) , doxorubicin ( 50 mg/m2 ) , and cyclophosphamide ( 500 mg/m2 ) ( PAC ) . PAC was administered monthly until disease progression or toxicity precluded additional therapy . Patients received a median of five treatment cycles ( range 1 - 13 ) . Of the 87 patients with measurable disease , 12 had a complete clinical response , while 27 had a partial clinical response , for an overall objective response rate of 45 % . No differences in response rates between primary and recurrent disease patients were noted . Median time to response was 2.5 months with a median response duration of 4.8 months . Nonresponders included 33 patients with stable disease and 15 with progression . Median progression-free survival for all patients was 6 months . Dose escalation was possible in 25 % of patients ; however , 52 % of patients required dose reductions during treatment . Clinical ly significant toxicities included neutropenia ( 65 % ) , anemia ( 47 % ) , emesis ( 21 % ) , nephrotoxicity ( 17 % ) , and neurotoxicity ( 4 % ) . Our study indicates that endometrial cancer is significantly responsive to PAC . Enthusiasm for this regimen should be tempered by the limited duration of response and substantial treatment toxicity 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 A phase II combination chemotherapy protocol combining methotrexate , vinblastine , doxorubicin , and cisplatin was design ed to evaluate tumor response and survival in patients with advanced/recurrent endometrial carcinoma . Thirty patients with advanced/recurrent endometrial carcinoma were assigned to chemotherapy treatment at 4-week intervals with methotrexate 30 mg/m2 i.v . Days 1 , 15 , and 22 ; vinblastine 3 mg/m2 i.v . Days 2 , 15 , and 22 ; doxorubicin 30 mg/m2 i.v . Day 2 ; and cisplatin 70 mg/m2 i.v . Day 2 . After a median of four cycles ( maximum number two cycles beyond complete regression ; minimum six cycles for stable partial regression ) , we observed objective regression in 20 patients ( 67 % ) ( 95 % CI , 50 , 84 ) with complete regression in 8 patients ( 27 % ) and partial regression in 12 patients ( 40 % ) . Median overall survival was 9.9 months ( range , 0.3 - 34.2 ) , and median survival of responders was 11.0 months ( range , 2.6 - 34.2 ) from initial date of response . Toxicity was substantial with two treatment-related deaths and consisted predominantly of neutropenia ( grade 3 or greater in 93 % of the patients ) , alopecia , nausea , emesis , stomatitis , and azotemia . In conclusion , MVAC is a highly active outpatient chemotherapy regimen in patients with advanced/recurrent endometrial carcinoma , achieving a high complete and partial response rate . Toxicity is substantial in this elderly patient population 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 Forty-nine consecutive patients with metastatic or recurrent endometrial carcinoma were treated with a monthly combination chemotherapy consisting of VP 16 - 213 80 mg/m2 i.v . Days 1 - 3 , 5-fluorouracil ( 5-FU ) 600 mg/m2 i.v . Days 1 - 3 , and cisplatin 35 mg/m2 i.v . Days 1 - 3 . The objective response rate was 41 % ( 95 % CI , 27 - 54 % ) with 14.3 % complete responses . The median survival duration was 14 months . The median response duration was 12 months . The estimated median survival for responders was 20 months . Three patients are still free of disease 5 years after treatment . The major toxic effects were myelosuppression ( less than 25 % of grade III and IV leucopenia , and 14 % grade III and IV thrombocytopenia ) . Grade III peripheral neuropathy was observed in five patients . Cisplatin administration had to be stopped due to renal toxicity in six patients . No treatment-related deaths occurred . The combination of etoposide , 5 fluorouracil , and cisplatin is an effective regimen with an acceptable toxicity in patients with recurrent or metastatic endometrial carcinoma PURPOSE To evaluate the toxic effects and antitumour activity of a multidrug regimen with cisplatin , epirubicin and paclitaxel ( CEP ) as initial therapy in patients with uterine adenocarcinoma . PATIENTS AND METHODS Forty-nine patients with histologically-confirmed diagnoses of locally advanced , recurrent or metastatic cervical or endometrial adenocarcinoma entered the study . Treatment consisted of epirubicin ( E ) given at 70 mg/m2 followed by paclitaxel ( P ) ( 175 mg/m2 over three hours ) and cisplatin ( C ) ( 50 mg/m2 ) , repeated every three weeks . Eligibility criteria also included age < or = 75 years , no previous chemotherapy , no previous radiotherapy to the tumour parameters , bidimensionally-measurable lesions , no previous or ongoing cardiac disease , and renal and liver function within normal limits .  Complete blood cell counts were repeated weekly , and tumor response was assessed every three cycles . A maximum of eight courses was administered in responding patients . RESULTS From January 1996 to January 1997 , 30 patients with endometrial adenocarcinoma and 19 with cervical adenocarcinoma entered the study , for a total of 213 cycles of treatment . In patients with endometrial carcinoma the overall clinical and pathological response rates were 73 % ( 95 % CI , range 54%-88 % ) and 35 % ( 95 % CI , range 16%-57 % ) respectively ; in patients with locally advanced cervical carcinoma the overall clinical and pathological response rates were 64 % and 62 % . WHO grade 3 - 4 neutropenia occurred in 61 % of the patients , with one possible toxic death . Retreatment had to be delayed for at least one week because of persisting neutropenia in 34 % of the patients . Mild peripheral neuropathy and stomatitis were observed in 46 % and 23 % of the patients . One patient presented acute congestive heart failure after the third cycle of treatment . CONCLUSION The high antitumour activity and the good tolerability of CEP  suggest that this regimen should be prospect ively compared to st and ard combinations as initial treatment of advanced endometrial carcinoma OBJECTIVE The aim of this study was to determine the effectiveness and toxicity of monthly treatment with intravenous paclitaxel for women with advanced or recurrent uterine papillary serous carcinoma ( UPSC ) . METHODS Consenting women with histologically confirmed advanced ( FIGO stage III or IV ) or recurrent UPSC were treated on an Institutional Review Board approved protocol of a 24-h intravenous infusion of 200 mg/m(2 ) of paclitaxel every 3 weeks . Both measurable and nonmeasurable disease cases were enrolled . Treatment was continued until disease progression , patient intolerance , or ( in women with nonmeasurable disease ) completion of six courses . RESULTS Twenty patients received from 1 to 11 cycles of therapy . Two women died of disease after 1 cycle of therapy and were not evaluable for response . Among 13 women with measurable tumor receiving 2 or more cycles of therapy , 4 had a complete clinical response and 6 had a partial response ( objective response rate , 77 % ) . The median time to progression was 7.3 months ( range , 2 - 21 months ) . All 3 remaining patients with measurable disease had stable disease for a median of 6 months . The 5 patients without evaluable disease received 5 to 6 cycles of adjuvant paclitaxel . Three developed recurrence ( range , 4 - 10 months ; median , 7.2 months ) . Neutropenia was the major toxicity . Eleven of the 20 patients required G-CSF support , and 9 were hospitalized for neutropenic fever . One woman had reversible cardiac symptoms , which might have been related to paclitaxel treatment . At the time of analysis ( mean follow-up , 23 months ; range , 4.3 - 59.9 months ) , 13 women had died of disease , 4 were alive with disease , and 2 were disease free . All 3 disease-free patients had been treated for nonmeasurable advanced stage disease . CONCLUSION Paclitaxel appears to have excellent activity in the treatment of advanced or recurrent UPSC , an uncommon but aggressive malignancy . Longer survival appears to be more common among women with small-volume disease PURPOSE To evaluate the efficacy of carboplatin plus paclitaxel in primarily advanced or recurrent endometrial cancers . PATIENTS AND METHO 
    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: Both single-agent cisplatin and the combination of doxorubicin and cyclophosphamide demonstrated moderate activity against endometrial carcinoma in earlier salvage trials . Since January 1979 , 102 patients with advanced primary ( n = 42 ) or recurrent ( n = 60 ) endometrial carcinoma were prospect ively treated with cisplatin ( 50 mg/m2 ) , doxorubicin ( 50 mg/m2 ) , and cyclophosphamide ( 500 mg/m2 ) ( PAC ) . PAC was administered monthly until disease progression or toxicity precluded additional therapy . Patients received a median of five treatment cycles ( range 1 - 13 ) . Of the 87 patients with measurable disease , 12 had a complete clinical response , while 27 had a partial clinical response , for an overall objective response rate of 45 % . No differences in response rates between primary and recurrent disease patients were noted . Median time to response was 2.5 months with a median response duration of 4.8 months . Nonresponders included 33 patients with stable disease and 15 with progression . Median progression-free survival for all patients was 6 months . Dose escalation was possible in 25 % of patients ; however , 52 % of patients required dose reductions during treatment . Clinical ly significant toxicities included neutropenia ( 65 % ) , anemia ( 47 % ) , emesis ( 21 % ) , nephrotoxicity ( 17 % ) , and neurotoxicity ( 4 % ) . Our study indicates that endometrial cancer is significantly responsive to PAC . Enthusiasm for this regimen should be tempered by the limited duration of response and substantial treatment toxicity 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 A phase II combination chemotherapy protocol combining methotrexate , vinblastine , doxorubicin , and cisplatin was design ed to evaluate tumor response and survival in patients with advanced/recurrent endometrial carcinoma . Thirty patients with advanced/recurrent endometrial carcinoma were assigned to chemotherapy treatment at 4-week intervals with methotrexate 30 mg/m2 i.v . Days 1 , 15 , and 22 ; vinblastine 3 mg/m2 i.v . Days 2 , 15 , and 22 ; doxorubicin 30 mg/m2 i.v . Day 2 ; and cisplatin 70 mg/m2 i.v . Day 2 . After a median of four cycles ( maximum number two cycles beyond complete regression ; minimum six cycles for stable partial regression ) , we observed objective regression in 20 patients ( 67 % ) ( 95 % CI , 50 , 84 ) with complete regression in 8 patients ( 27 % ) and partial regression in 12 patients ( 40 % ) . Median overall survival was 9.9 months ( range , 0.3 - 34.2 ) , and median survival of responders was 11.0 months ( range , 2.6 - 34.2 ) from initial date of response . Toxicity was substantial with two treatment-related deaths and consisted predominantly of neutropenia ( grade 3 or greater in 93 % of the patients ) , alopecia , nausea , emesis , stomatitis , and azotemia . In conclusion , MVAC is a highly active outpatient chemotherapy regimen in patients with advanced/recurrent endometrial carcinoma , achieving a high complete and partial response rate . Toxicity is substantial in this elderly patient population 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 Forty-nine consecutive patients with metastatic or recurrent endometrial carcinoma were treated with a monthly combination chemotherapy consisting of VP 16 - 213 80 mg/m2 i.v . Days 1 - 3 , 5-fluorouracil ( 5-FU ) 600 mg/m2 i.v . Days 1 - 3 , and cisplatin 35 mg/m2 i.v . Days 1 - 3 . The objective response rate was 41 % ( 95 % CI , 27 - 54 % ) with 14.3 % complete responses . The median survival duration was 14 months . The median response duration was 12 months . The estimated median survival for responders was 20 months . Three patients are still free of disease 5 years after treatment . The major toxic effects were myelosuppression ( less than 25 % of grade III and IV leucopenia , and 14 % grade III and IV thrombocytopenia ) . Grade III peripheral neuropathy was observed in five patients . Cisplatin administration had to be stopped due to renal toxicity in six patients . No treatment-related deaths occurred . The combination of etoposide , 5 fluorouracil , and cisplatin is an effective regimen with an acceptable toxicity in patients with recurrent or metastatic endometrial carcinoma PURPOSE To evaluate the toxic effects and antitumour activity of a multidrug regimen with cisplatin , epirubicin and paclitaxel ( CEP ) as initial therapy in patients with uterine adenocarcinoma . PATIENTS AND METHODS Forty-nine patients with histologically-confirmed diagnoses of locally advanced , recurrent or metastatic cervical or endometrial adenocarcinoma entered the study . Treatment consisted of epirubicin ( E ) given at 70 mg/m2 followed by paclitaxel ( P ) ( 175 mg/m2 over three hours ) and cisplatin ( C ) ( 50 mg/m2 ) , repeated every three weeks . Eligibility criteria also included age < or = 75 years , no previous chemotherapy , no previous radiotherapy to the tumour parameters , bidimensionally-measurable lesions , no previous or ongoing cardiac disease , and renal and liver function within normal limits .  Complete blood cell counts were repeated weekly , and tumor response was assessed every three cycles . A maximum of eight courses was administered in responding patients . RESULTS From January 1996 to January 1997 , 30 patients with endometrial adenocarcinoma and 19 with cervical adenocarcinoma entered the study , for a total of 213 cycles of treatment . In patients with endometrial carcinoma the overall clinical and pathological response rates were 73 % ( 95 % CI , range 54%-88 % ) and 35 % ( 95 % CI , range 16%-57 % ) respectively ; in patients with locally advanced cervical carcinoma the overall clinical and pathological response rates were 64 % and 62 % . WHO grade 3 - 4 neutropenia occurred in 61 % of the patients , with one possible toxic death . Retreatment had to be delayed for at least one week because of persisting neutropenia in 34 % of the patients . Mild peripheral neuropathy and stomatitis were observed in 46 % and 23 % of the patients . One patient presented acute congestive heart failure after the third cycle of treatment . CONCLUSION The high antitumour activity and the good tolerability of CEP  suggest that this regimen should be prospect ively compared to st and ard combinations as initial treatment of advanced endometrial carcinoma OBJECTIVE The aim of this study was to determine the effectiveness and toxicity of monthly treatment with intravenous paclitaxel for women with advanced or recurrent uterine papillary serous carcinoma ( UPSC ) . METHODS Consenting women with histologically confirmed advanced ( FIGO stage III or IV ) or recurrent UPSC were treated on an Institutional Review Board approved protocol of a 24-h intravenous infusion of 200 mg/m(2 ) of paclitaxel every 3 weeks . Both measurable and nonmeasurable disease cases were enrolled . Treatment was continued until disease progression , patient intolerance , or ( in women with nonmeasurable disease ) completion of six courses . RESULTS Twenty patients received from 1 to 11 cycles of therapy . Two women died of disease after 1 cycle of therapy and were not evaluable for response . Among 13 women with measurable tumor receiving 2 or more cycles of therapy , 4 had a complete clinical response and 6 had a partial response ( objective response rate , 77 % ) . The median time to progression was 7.3 months ( range , 2 - 21 months ) . All 3 remaining patients with measurable disease had stable disease for a median of 6 months . The 5 patients without evaluable disease received 5 to 6 cycles of adjuvant paclitaxel . Three developed recurrence ( range , 4 - 10 months ; median , 7.2 months ) . Neutropenia was the major toxicity . Eleven of the 20 patients required G-CSF support , and 9 were hospitalized for neutropenic fever . One woman had reversible cardiac symptoms , which might have been related to paclitaxel treatment . At the time of analysis ( mean follow-up , 23 months ; range , 4.3 - 59.9 months ) , 13 women had died of disease , 4 were alive with disease , and 2 were disease free . All 3 disease-free patients had been treated for nonmeasurable advanced stage disease . CONCLUSION Paclitaxel appears to have excellent activity in the treatment of advanced or recurrent UPSC , an uncommon but aggressive malignancy . Longer survival appears to be more common among women with small-volume disease PURPOSE To evaluate the efficacy of carboplatin plus paclitaxel in primarily advanced or recurrent endometrial cancers . PATIENTS AND METHO 
    Output:
    