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: The Qualitator is a daily diary card to measure Quality of Life , developed for use in chemotherapy trials for patients with advanced breast cancer . In a trial at King 's College Hospital , 29 patients completed the Qualitator  and their scores were compared with scores in the Linear Analogue Self- Assessment and Nottingham Health Profile taken four-weekly . In a separate study at Guy 's Hospital , 31 patients completed the diary . The Qualitator offers accurate prognostic data regarding subsequent UICC response and survival and is simple to use PURPOSE To compare the efficacy of pegylated liposomal doxorubicin ( PLD ) with that of a common salvage regimen ( comparator ) in patients with taxane-refractory advanced breast cancer . PATIENTS AND METHODS Following failure of a first- or second-line  taxane-containing regimen for metastatic disease , 301 women were r and omly assigned to receive PLD ( 50 mg/m(2 ) every 28 days ) ; or comparator-vinorelbine ( 30 mg/m(2 ) weekly ) or mitomycin C ( 10 mg/m(2 ) day 1 and every 28 days ) plus vinblastine ( 5 mg/m(2 ) day 1 , day 14 , day 28 , and day 42 ) every 6 to 8 weeks . Patients were stratified before r and om assignment based on number of previous chemotherapy regimens for metastatic disease and presence of bone metastases only . RESULTS Progression-free survival ( PFS ) and overall survival ( OS ) were similar for PLD and comparator ( PFS : hazard ratio [ HR ] , 1.26 ; 95 % CI , 0.98 to 1.62 ; P = .11 ; median , 2.9 months [ PLD ] and 2.5 months [ comparator ] ; OS : HR , 1.05 ; 95 % CI , 0.82 to 1.33 ; P = .71 ; median , 11.0 months [ PLD ] and 9.0 months [ comparator ] ) . In anthracycline-naïve patients , PFS was somewhat longer with PLD , relative to the comparator ( n = 44 ; median PFS , 5.8 v 2.1 months ; HR , 2.40 ; 95 % CI , 1.16 to 4.95 ; P = .01 ) . Most frequently reported adverse events were nausea ( 23 % to 31 % ) , vomiting ( 17 % to 20 % ) , and fatigue ( 9 % to 20 % ) and were similar among treatment groups . PLD-treated patients experienced more palmar-plantar erythrodysesthesia ( 37 % ; 18 % grade 3 , 1 patient grade 4 ) and stomatitis ( 22 % ; 5 % grade s 3/4 ) . Neuropathy ( 11 % ) , constipation ( 16 % ) , and neutropenia ( 14 % ) were more common with vinorelbine . Alopecia was low in both the PLD and vinorelbine groups ( 3 % and 5 % ) . CONCLUSION PLD has efficacy comparable to that of common salvage regimens in patients with taxane-refractory metastatic breast cancer , thereby representing a useful therapeutic option 39 previously treated patients with metastatic breast cancer were treated in a partially r and omized study evaluating VP-16 and the combination of Vincristine ( VCR ) and Adriamycin ( ADR ) . Of the 19 patients treated with VP-16  initially , two had partial remissions . No responses were noted in eleven patients who corssed-over after failing VCR plus ADR . Of the 20 patients treated with VCR plus ADR initially , four patients had partial responses . An additional 2/15 patients responded on crossover after failing initially on VP-16 . No significant differences in time to last follow-up or death could be detected between the two treatment programs Forty patients with advanced breast cancer , r and omised to receive CMF or weekly low dose Epirubicin  , were evaluated by UICC criteria of response and WHO toxicity criteria , in addition to three QoL instruments : the ' Qualitator ' daily diary card , 4 weekly Nottingham Health Profile ( NHP ) and Linear Analogue Self- Assessment ( LASA ) . Response rates were 58 % for CMF and 29 % for epirubicin ( chi 2 = 3.51 , 1 d.f . , P > 0.05 ) . Median time to treatment failure was 24 weeks for CMF , 7 weeks for epirubicin ( P < 0.05 ) but survival was similar in both groups . Survival was better for responders than for non-responders ( medians 87 and 30 weeks , P = 0.02 ) . CMF caused more objective alopecia ( P < 0.001 ) , nausea and vomiting ( P < 0.001 ) and haematological toxicity ( P < 0.02 ) . However , QoL measures only recorded a significant difference in energy and pain , influenced primarily by the non-responders in each treatment group but with no difference in overall global scores . Scores for responders , irrespective of treatment , were better to start with ( LASA P = 0.001 ) ; at 12 weeks , scores had improved ( Qualitator P < 0.05 ; NHP P < 0.05 ) . Scores in non-responders showed no change . In this small study aggressive chemotherapy gave better response and similar survival without impairing Quality of life overall . Detailed QoL measurement should be integral to all cancer chemotherapy trials One hundred twenty-two patients with advanced adenocarcinoma of the breast were r and omized to receive adriamycin ( AD ) alone or a combination of VP-16 plus lower dose adriamycin ( VAD ) . The patients were stratified to good and poor risk . The starting dose ( day 1 ) of AD was 60 mg/m2 for good risk and 45 mg/m2 for poor risk . The starting dose of the VAD combination for the good-risk patient was VP-16 , 75 mg/m2 daily x 5 plus adriamycin 35 mg/m2 . The poor-risk dose for VAD was VP-16 , 50 mg/m2 daily x 5 plus adriamycin , 30 mg/m2 on day 1 . The total dose of AD was 450 mg/m2 on both arms . The patients who were on the VAD arm continued on VP-16 maintenance . Both arms were repeated every 21 days . There were 54 evaluable patients on the adriamycin arm and 52 evaluable patients on the VAD arm . Both arms were similar with regard to age , menopausal status , performance status , and prior hormonal therapy . More hematologic toxicity was seen in the adriamycin arm . Complete responses were observed on both arms , three ( 5 % ) with adriamycin and three ( 5 % ) with combination . Eleven ( 19 % ) and ten ( 18 % ) partial responses were observed with the adriamycin and VP-16 plus adriamycin , respectively . AD produced more stable disease than VAD ( 41 % vs. 29 % ) . Complete responses were seen only in the good-risk patients . Time to progression was delayed on the combination arm ( P = 0.02 ) . The survival in both arms was similar . The addition of VP-16 to adriamycin does not offer an important clinical advantage Since current clinical trials assessing new agents occur in patients with advanced breast cancer having failed one and sometimes many polychemotherapy programs , these new agents may not be given a fair trial . In an effort to assess the possibility of using an alternative study design , we analyzed older clinical trials that used a controlled study design , r and omizing between a single new drug and an established polychemotherapy program with a cross-over design upon failure . We were interested in noting that the pooled data did display a slight survival advantage ( median 3.7 months ) for the group receiving  polychemotherapy  as initial therapy . The survival distributions were clearly not significant using the log rank test , but did approach significance using the Smirnov . It is apparent that , while some slight advantage does occur for that group of patients receiving initial polychemotherapy , the magnitude of this effect is not great and is short in duration . Serious consideration should be given to the assessment of new agents as first-line therapy , particularly should they have a unique mode of action or lessened morbidities or toxicities Purpose : To compare the efficacy and toxicity of epirubicin to that of the combination of epirubicin and cisplatin in patients with advanced breast cancer . Patients and methods : A total of 155 patients were r and omized to receive either epirubicin ( 70 mg/m2 ) days 1 and 8 every 4 weeks or epirubicin ( 60 mg/m2 ) days 1 and 8 plus cisplatin ( 100 mg/m2 ) day 1 every 4 weeks . Epirubicin was continued until disease progression or to a cumulative dose of 1000 mg/m2 . Cisplatin was discontinued after six cycles . In 45 premenopausal women an oophorectomy was performed . None of the evaluable patients had received chemotherapy for metastatic disease . Results : Among evaluable patients ( 74 in the epirubicin group and 65 in the epirubicin plus cisplatin group ) there were 19 % vs 29 % complete responses , and 42 % vs 37 % partial responses , with no significant difference . In the epirubicin plus cisplatin group the response rate was significantly higher in previously untreated patients as compared with patients who had received adjuvant chemotherapy ( 74 % vs 55 % , P=0.002 ) . Median times to disease progression were 8.4 months in the epirubicin group and 15.3 months in the epirubicin plus cisplatin group ( P=0.045 ) . Median survival times were 15.1 and 21.5 months , respectively ( P=0.41 ) . In the epirubicin plus cisplatin group leukopenia and thrombocytopenia were significantly more frequent , 29 % of the patients developed mild to moderate peripheral neurotoxicity , 34 % reported tinnitus and hearing changes , 6 patients developed nephrotoxicity ( one died due to nephrotic syndrome ) , and 3 patients developed leukaemia ( two died of this cause ) . Congestive heart failure occurred in six patients in the epirubicin group and three patients in the epirubicin plus cisplatin group . Conclusion : Cisplatin plus epirubicin is an active , although highly toxic regimen when used as first-line therapy in advanced breast cancer . The time to disease progression was significantly longer in the cisplatin plus epirubicin group ( increased by 82 % ) . Due to toxicity , the combination regimen can not be recommended . However , the study indicated a very high activity of cisplatin in advanced breast cancer . Studies of first-line therapy in advanced breast cancer including cisplatin or other platin derivatives in combination with , for example , the taxanes are suggested Our objective was to determine whether oral etoposide and cisplatin combination ( EoP ) is superior to paclitaxel in the treatment of advanced breast cancer ( ABC ) patients pretreated with anthracyclines . From December 1997 to August 2003 , 201 patients were r and omised , 100 to EoP and 101 to paclitaxel arms . Four patients in each arm were ineligible . The doses of etoposide and cisplatin were 50 mg p.o . twice a day for 7 days and 70 mg m−2 intravenously ( i.v . ) on day 1 , respectively , and it was 175 mg m−2 on day 1 for paclitaxel . Both treatments were repeated every 3 weeks . A median of four cycles of study treatment was given in both arms . The response rate obtained in the EoP arm was significantly higher ( 36.3 vs 22.2 % ; P=0.038 ) . Median response duration was longer for the EoP arm ( 7 vs 4 months ) ( P=0.132 ) . Also , time to progression was significantly in favour of the EoP arm ( 5.5 vs 3.9 months ; P=0.003 ) . Median overall survival was again significantly longer in the EoP arm ( 14 vs 9.5 months ; P=0.039 ) . Toxicity profile of both groups was similar . Two patients in each arm were lost due to febrile neutropenia . The observed activity and acceptable toxicity of EoP endorses the employment of this combination in the treatment of ABC following anthracyclines A double blind study to compare the efficacy of oral UFT ( 400 mg Tegafur ( FT ) plus 896 mg uracil/day ) with that of oral FT ( 800 mg/day ) on advanced breast cancer was performed between November , 1986 , and November , 1989 . Sixty patients were registered for the trial and fifty-six cases were evaluated ( 28 for UFT and 28 for FT ) . The primary end points in the study were response rate and time to relapse . There were no significant differences in patients ' characteristics in either group . The objective response rates were 39 % ( 11/28 ; 95 % confidence interval ( C.I. ) , 22 - 59 % ) in UFT and 21 % ( 6/28 ; 95 % C.I. , 8 - 41 % ) in FT , without statistical significance ( P = 0.25 ) . For time to relapse , a trend was seen in favor of UFT , but this effect did not achieve 
    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: The Qualitator is a daily diary card to measure Quality of Life , developed for use in chemotherapy trials for patients with advanced breast cancer . In a trial at King 's College Hospital , 29 patients completed the Qualitator  and their scores were compared with scores in the Linear Analogue Self- Assessment and Nottingham Health Profile taken four-weekly . In a separate study at Guy 's Hospital , 31 patients completed the diary . The Qualitator offers accurate prognostic data regarding subsequent UICC response and survival and is simple to use PURPOSE To compare the efficacy of pegylated liposomal doxorubicin ( PLD ) with that of a common salvage regimen ( comparator ) in patients with taxane-refractory advanced breast cancer . PATIENTS AND METHODS Following failure of a first- or second-line  taxane-containing regimen for metastatic disease , 301 women were r and omly assigned to receive PLD ( 50 mg/m(2 ) every 28 days ) ; or comparator-vinorelbine ( 30 mg/m(2 ) weekly ) or mitomycin C ( 10 mg/m(2 ) day 1 and every 28 days ) plus vinblastine ( 5 mg/m(2 ) day 1 , day 14 , day 28 , and day 42 ) every 6 to 8 weeks . Patients were stratified before r and om assignment based on number of previous chemotherapy regimens for metastatic disease and presence of bone metastases only . RESULTS Progression-free survival ( PFS ) and overall survival ( OS ) were similar for PLD and comparator ( PFS : hazard ratio [ HR ] , 1.26 ; 95 % CI , 0.98 to 1.62 ; P = .11 ; median , 2.9 months [ PLD ] and 2.5 months [ comparator ] ; OS : HR , 1.05 ; 95 % CI , 0.82 to 1.33 ; P = .71 ; median , 11.0 months [ PLD ] and 9.0 months [ comparator ] ) . In anthracycline-naïve patients , PFS was somewhat longer with PLD , relative to the comparator ( n = 44 ; median PFS , 5.8 v 2.1 months ; HR , 2.40 ; 95 % CI , 1.16 to 4.95 ; P = .01 ) . Most frequently reported adverse events were nausea ( 23 % to 31 % ) , vomiting ( 17 % to 20 % ) , and fatigue ( 9 % to 20 % ) and were similar among treatment groups . PLD-treated patients experienced more palmar-plantar erythrodysesthesia ( 37 % ; 18 % grade 3 , 1 patient grade 4 ) and stomatitis ( 22 % ; 5 % grade s 3/4 ) . Neuropathy ( 11 % ) , constipation ( 16 % ) , and neutropenia ( 14 % ) were more common with vinorelbine . Alopecia was low in both the PLD and vinorelbine groups ( 3 % and 5 % ) . CONCLUSION PLD has efficacy comparable to that of common salvage regimens in patients with taxane-refractory metastatic breast cancer , thereby representing a useful therapeutic option 39 previously treated patients with metastatic breast cancer were treated in a partially r and omized study evaluating VP-16 and the combination of Vincristine ( VCR ) and Adriamycin ( ADR ) . Of the 19 patients treated with VP-16  initially , two had partial remissions . No responses were noted in eleven patients who corssed-over after failing VCR plus ADR . Of the 20 patients treated with VCR plus ADR initially , four patients had partial responses . An additional 2/15 patients responded on crossover after failing initially on VP-16 . No significant differences in time to last follow-up or death could be detected between the two treatment programs Forty patients with advanced breast cancer , r and omised to receive CMF or weekly low dose Epirubicin  , were evaluated by UICC criteria of response and WHO toxicity criteria , in addition to three QoL instruments : the ' Qualitator ' daily diary card , 4 weekly Nottingham Health Profile ( NHP ) and Linear Analogue Self- Assessment ( LASA ) . Response rates were 58 % for CMF and 29 % for epirubicin ( chi 2 = 3.51 , 1 d.f . , P > 0.05 ) . Median time to treatment failure was 24 weeks for CMF , 7 weeks for epirubicin ( P < 0.05 ) but survival was similar in both groups . Survival was better for responders than for non-responders ( medians 87 and 30 weeks , P = 0.02 ) . CMF caused more objective alopecia ( P < 0.001 ) , nausea and vomiting ( P < 0.001 ) and haematological toxicity ( P < 0.02 ) . However , QoL measures only recorded a significant difference in energy and pain , influenced primarily by the non-responders in each treatment group but with no difference in overall global scores . Scores for responders , irrespective of treatment , were better to start with ( LASA P = 0.001 ) ; at 12 weeks , scores had improved ( Qualitator P < 0.05 ; NHP P < 0.05 ) . Scores in non-responders showed no change . In this small study aggressive chemotherapy gave better response and similar survival without impairing Quality of life overall . Detailed QoL measurement should be integral to all cancer chemotherapy trials One hundred twenty-two patients with advanced adenocarcinoma of the breast were r and omized to receive adriamycin ( AD ) alone or a combination of VP-16 plus lower dose adriamycin ( VAD ) . The patients were stratified to good and poor risk . The starting dose ( day 1 ) of AD was 60 mg/m2 for good risk and 45 mg/m2 for poor risk . The starting dose of the VAD combination for the good-risk patient was VP-16 , 75 mg/m2 daily x 5 plus adriamycin 35 mg/m2 . The poor-risk dose for VAD was VP-16 , 50 mg/m2 daily x 5 plus adriamycin , 30 mg/m2 on day 1 . The total dose of AD was 450 mg/m2 on both arms . The patients who were on the VAD arm continued on VP-16 maintenance . Both arms were repeated every 21 days . There were 54 evaluable patients on the adriamycin arm and 52 evaluable patients on the VAD arm . Both arms were similar with regard to age , menopausal status , performance status , and prior hormonal therapy . More hematologic toxicity was seen in the adriamycin arm . Complete responses were observed on both arms , three ( 5 % ) with adriamycin and three ( 5 % ) with combination . Eleven ( 19 % ) and ten ( 18 % ) partial responses were observed with the adriamycin and VP-16 plus adriamycin , respectively . AD produced more stable disease than VAD ( 41 % vs. 29 % ) . Complete responses were seen only in the good-risk patients . Time to progression was delayed on the combination arm ( P = 0.02 ) . The survival in both arms was similar . The addition of VP-16 to adriamycin does not offer an important clinical advantage Since current clinical trials assessing new agents occur in patients with advanced breast cancer having failed one and sometimes many polychemotherapy programs , these new agents may not be given a fair trial . In an effort to assess the possibility of using an alternative study design , we analyzed older clinical trials that used a controlled study design , r and omizing between a single new drug and an established polychemotherapy program with a cross-over design upon failure . We were interested in noting that the pooled data did display a slight survival advantage ( median 3.7 months ) for the group receiving  polychemotherapy  as initial therapy . The survival distributions were clearly not significant using the log rank test , but did approach significance using the Smirnov . It is apparent that , while some slight advantage does occur for that group of patients receiving initial polychemotherapy , the magnitude of this effect is not great and is short in duration . Serious consideration should be given to the assessment of new agents as first-line therapy , particularly should they have a unique mode of action or lessened morbidities or toxicities Purpose : To compare the efficacy and toxicity of epirubicin to that of the combination of epirubicin and cisplatin in patients with advanced breast cancer . Patients and methods : A total of 155 patients were r and omized to receive either epirubicin ( 70 mg/m2 ) days 1 and 8 every 4 weeks or epirubicin ( 60 mg/m2 ) days 1 and 8 plus cisplatin ( 100 mg/m2 ) day 1 every 4 weeks . Epirubicin was continued until disease progression or to a cumulative dose of 1000 mg/m2 . Cisplatin was discontinued after six cycles . In 45 premenopausal women an oophorectomy was performed . None of the evaluable patients had received chemotherapy for metastatic disease . Results : Among evaluable patients ( 74 in the epirubicin group and 65 in the epirubicin plus cisplatin group ) there were 19 % vs 29 % complete responses , and 42 % vs 37 % partial responses , with no significant difference . In the epirubicin plus cisplatin group the response rate was significantly higher in previously untreated patients as compared with patients who had received adjuvant chemotherapy ( 74 % vs 55 % , P=0.002 ) . Median times to disease progression were 8.4 months in the epirubicin group and 15.3 months in the epirubicin plus cisplatin group ( P=0.045 ) . Median survival times were 15.1 and 21.5 months , respectively ( P=0.41 ) . In the epirubicin plus cisplatin group leukopenia and thrombocytopenia were significantly more frequent , 29 % of the patients developed mild to moderate peripheral neurotoxicity , 34 % reported tinnitus and hearing changes , 6 patients developed nephrotoxicity ( one died due to nephrotic syndrome ) , and 3 patients developed leukaemia ( two died of this cause ) . Congestive heart failure occurred in six patients in the epirubicin group and three patients in the epirubicin plus cisplatin group . Conclusion : Cisplatin plus epirubicin is an active , although highly toxic regimen when used as first-line therapy in advanced breast cancer . The time to disease progression was significantly longer in the cisplatin plus epirubicin group ( increased by 82 % ) . Due to toxicity , the combination regimen can not be recommended . However , the study indicated a very high activity of cisplatin in advanced breast cancer . Studies of first-line therapy in advanced breast cancer including cisplatin or other platin derivatives in combination with , for example , the taxanes are suggested Our objective was to determine whether oral etoposide and cisplatin combination ( EoP ) is superior to paclitaxel in the treatment of advanced breast cancer ( ABC ) patients pretreated with anthracyclines . From December 1997 to August 2003 , 201 patients were r and omised , 100 to EoP and 101 to paclitaxel arms . Four patients in each arm were ineligible . The doses of etoposide and cisplatin were 50 mg p.o . twice a day for 7 days and 70 mg m−2 intravenously ( i.v . ) on day 1 , respectively , and it was 175 mg m−2 on day 1 for paclitaxel . Both treatments were repeated every 3 weeks . A median of four cycles of study treatment was given in both arms . The response rate obtained in the EoP arm was significantly higher ( 36.3 vs 22.2 % ; P=0.038 ) . Median response duration was longer for the EoP arm ( 7 vs 4 months ) ( P=0.132 ) . Also , time to progression was significantly in favour of the EoP arm ( 5.5 vs 3.9 months ; P=0.003 ) . Median overall survival was again significantly longer in the EoP arm ( 14 vs 9.5 months ; P=0.039 ) . Toxicity profile of both groups was similar . Two patients in each arm were lost due to febrile neutropenia . The observed activity and acceptable toxicity of EoP endorses the employment of this combination in the treatment of ABC following anthracyclines A double blind study to compare the efficacy of oral UFT ( 400 mg Tegafur ( FT ) plus 896 mg uracil/day ) with that of oral FT ( 800 mg/day ) on advanced breast cancer was performed between November , 1986 , and November , 1989 . Sixty patients were registered for the trial and fifty-six cases were evaluated ( 28 for UFT and 28 for FT ) . The primary end points in the study were response rate and time to relapse . There were no significant differences in patients ' characteristics in either group . The objective response rates were 39 % ( 11/28 ; 95 % confidence interval ( C.I. ) , 22 - 59 % ) in UFT and 21 % ( 6/28 ; 95 % C.I. , 8 - 41 % ) in FT , without statistical significance ( P = 0.25 ) . For time to relapse , a trend was seen in favor of UFT , but this effect did not achieve 
    Output:
    