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 Forty‐nine patients with advanced carcinoma of the breast who had received no prior chemotherapy were r and omized to receive either high‐dose cyclophosphamide ( C ) 1250 mg/M2 intravenously on day 1 and 5‐fluorouracil ( F ) 600 mg/M2 intravenously on days 1 through 5 ( CF ) , or vincristine ( V ) 1.5 mg/M2 , doxorubicin ( A ) 50 mg/M2 and cyclophosphamide ( C ) 500 mg/M2 ( VAC ) , all intravenously on day 1 . Both regimens were repeated at 3‐week intervals . Nine of 25 patients ( 36 % ) treated with CF and ten of 21 patients ( 48 % ) treated with VAC showed a complete or partial response as defined by the ( UICC ) guidelines . The estimated median time to progression for all patients was 3.5 months for CF and 6.0 months for VAC , with the median time to progression for responding patients being 8.5 months on CF and 6.3 months on VAC . Estimated survival is also similar for the two regimens . Ten of the patients treated with high‐dose CF experienced septic episodes and four died . Toxicity on the CF arm necessitated premature closure of the study , and thus full statistical comparison of the efficacy of the two regimens can not be made Summary From October 1973 to October 1977 the ECOG prospect ively evaluated cyclophosphamide , methotrexate , and fluorouracil ( CMF ) versus CMF plus fluoxymesterone ( CMFH ) maintenance therapies in responders to 6 months of induction therapy which consisted of either CMF , CMF plus prednisone ( CMFP ) , or adriamycin plus vincristine ( AV ) . Following the maintenance r and omization 12 % of the patients converted from a PR to a CR status . The median time from r and omization to treatment failure was 9.5 months for CMFH and 6.7 months for CMF ( p = 0.03 ) . This difference was observed only for partial responders ( p = 0.01 ) and not for complete responders . Patients receiving CMFH  tended to maintain higher hemoglobin , leukocyte , and platelet levels , and receive a higher dosage of each of the cytotoxic drugs . The results are taken as evidence that the addition of fluoxymesterone to a maintenance CMF regimen provides a therapeutic advantage . It is hypothesized that this effect is due at least in part to fluoxymesterone associated maintenance of improved marrow function result ing in greater myelosuppressive drug delivery 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 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 A prospect i ve study with two cytotoxic combinations ( cyclophosphamide , methotrexate , and fluorouracil ( CMF ) , and adriamycin plus vincristine ( AV ) ) was carried out in 110 patients with advanced breast cancer . There was no significant difference between the treatment groups in the response rate after primary treatment , the median duration of response , and the median survival . In both groups responders survived for longer than non-responders . Secondary treatment after crossover for progression or relapse result ed in response rates of 35 % for AV and 20 % for CMF .  Toxicity was mainly represented by reversible haemosuppression . These results are comparable with those obtained with other multiple-drug regimens , and combination chemotherapy alone seems to have reached a plateau in its capacity to control disseminated breast cancer The prospect i ve controlled Phase III clinical trial tested the therapeutic value of the cis-platinum-adriamycin-cyclophosphamide combination ( CAP ) , compared with the combination including cyclophosphamide , methotrexate , 5-fluorouracil , vincristine and prednisolone ( CMFVP ) , in untreated metastatic breast cancer . One hundred and twenty-three patients ( > 2 cycles ) were evaluated : 61 on the CAP , and 62 on the CMFVP schedule .  An objective response ( CR+PR ) to CAP combination chemotherapy was achieved in 72 % of patients ( 43/61 ) , with a high rate ( 36 % ) of complete remissions . In terms of metastatic site , the response rate appeared to be particularly high in soft tissue and visceral organ ( lung , liver ) metastases . In the CMFVP group , an objective response was noted in 26 of 62 patients ( 42 % ) , with 16 % complete remissions . The difference in overall therapeutic response - and in the complete remission rate as well - was statistically significant to the advantage of the CAP regimen ( P < 0.01 ) . The duration of remissions was 6 - 28 + months ( mean = 14 ) for the CAP , and 4 - 15 + months ( mean = 9 ) for the CMFVP schedule . Toxic side effects were more pronounced in the CAP group , particularly myelosuppression , with anemia prevailing . Side effects to CMFVP treatment were moderate . In 39 CMFVP previously treated cases , CAP was administered as second-line treatment , and an objective response was observed in 51 % of cases ( 20/39 ) . Results of this controlled trial showed the advantage of the CAP combination chemotherapy in the treatment of metastatic breast cancer Summary One hundred and sixteen patients with locally advanced or metastatic breast cancer were r and omized to receive CMF ( cyclophosphamide 600 mg m–2 day 1 and 8 i.v . , 5-fluorouracil 600 mg m–2 day 1 and 8 i.v . , , methotrexate 40 mg m–2 day 1 and 8 i.v . , monthly for 6 cycles ) or MM ( methotrexate 30 mg m–2 , mitoxantrone 6.5 mg m–2 , both i.v . day 1 3-weekly for 8 cycles ) as first line treatment with chemotherapy .  Objective responses occurred in 17 patients out of 58 ( 29 % ) who received CMF and nine out of 58 ( 15 % ) who received MM ; 95 % confidence interval for difference in response rates ( –1%–29 % ) , P = 0.07 . No statistically significant differences were seen in overall survival or time to progression between the two regimes although a tendency towards a shorter progression time on the MM regime must be acknowledged . There was , however , significantly reduced haematological toxicity ( P < 0.001 ) and alopecia ( P < 0.001 ) and fewer dose reductions and delays in patients r and omized to MM . No statistically significant differences were seen between the two regimes in terms of quality of life ( QOL ) . However , some association between QOL and toxicity was apparent overall with pooled QOL estimates tending to indicate a worsening in psychological state with increasing maximum toxicity over treatment . Despite the fact that results surrounding response rates and time to progression did not reach statistical significance , their possible compatibility with an improved outcome on CMF treatment must be borne in mind . However , MM is a well-tolerated regimen with fewer side-effects than CMF , which with careful patient management and follow-up , therefore , may merit consideration as a first-line treatment to palliate patients with metastatic breast cancer who are infirm or elderly Identification of important prognostic factors with respect to the patient 's initial response to therapy was made from a set of 25 covariates available on 281 patients with advanced breast cancer . Since the patients studied were all participants in a r and omized clinical trial that involved three different treatment regimens ( repeated weekly treatment of a combination of cyclophosphamide , methotrexate , 5-fluorouracil , vincristine , and prednisone ; intermittent treatment of the same preceding five drugs given in 5-day courses every 4 weeks ; or treatment every 3 weeks with adriamycin as a single agent ) , the effect of these treatments on the selection of important covariates was assessed . Although some evidence indicated that the set of important covariates differed by treatment , the differences were not strong enough to be of practical importance . Non-Caucasian patients did poorly on all regimens with a response rate of only 31 % compared to 62 % for Caucasian patients . The covariates of major prognostic importance for Caucasians were : disease-free interval , liver involvement , and performance status . Ambulatory patients with long disease-free intervals and no liver involvement had the best prognosis . After adjustments were made for these three covariates , the remaining covariates ( such as menopausal status , bone involvement , number of metastatic sites , and duration of metastatic disease ) were not significantly related to response . As reported earlier , the treatment effect was significant , even after adjustments were made for the important covariates BACKGROUND To compare survival between patients with advanced breast cancer ( ABC ) treated with epirubicin/paclitaxel ( Taxol ) or paclitaxel/carboplatin ( Cp ) chemotherapy . PATIENTS AND METHODS From January 1999 to April 2002 , 327 eligible patients with ABC were r and omized to receive either paclitaxel 175 mg/m(2 ) in a 3-h infusion followed by epirubicin ( EPI ) 80 mg/m(2 ) ( group A ) or paclitaxel , as in group A , followed by Cp at an AUC of 6 mg x min/ml ( group B ) every 3 weeks for six cycles . RESULTS After a median follow-up of 23.5 months , median survival was not significantly different between the two groups ( 22.4 months versus 27.8 months , P=0.25 ) , whereas median time to treatment failure was significantly longer in patients treated with paclitaxel/Cp ( 8.1 months in group A versus 10.8 months in group B , P=0.04 ) . Both regimens were well tolerated . In total , 39 patients ( 24 % ) in group A and 46 ( 29 % ) in group B suffered at least one severe side-effect . Quality -of-life assessment and cost analysis did not reveal any significant differences between the two groups . CONCLUSION Our study suggests that the paclitaxel/Cp combination is an effective therapeutic alternative for patients with ABC in which anthracycline administration has the potential of being harmful To evaluate the substitution of methotrexate with doxorubicin ( Dox ) in CMF-(cyclophosphamide , methotrexate , 5-fluorouracil ) containing regimen for advanced breast cancer , 415 postmenopausal patients below the age of 66 years , na 
    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 Forty‐nine patients with advanced carcinoma of the breast who had received no prior chemotherapy were r and omized to receive either high‐dose cyclophosphamide ( C ) 1250 mg/M2 intravenously on day 1 and 5‐fluorouracil ( F ) 600 mg/M2 intravenously on days 1 through 5 ( CF ) , or vincristine ( V ) 1.5 mg/M2 , doxorubicin ( A ) 50 mg/M2 and cyclophosphamide ( C ) 500 mg/M2 ( VAC ) , all intravenously on day 1 . Both regimens were repeated at 3‐week intervals . Nine of 25 patients ( 36 % ) treated with CF and ten of 21 patients ( 48 % ) treated with VAC showed a complete or partial response as defined by the ( UICC ) guidelines . The estimated median time to progression for all patients was 3.5 months for CF and 6.0 months for VAC , with the median time to progression for responding patients being 8.5 months on CF and 6.3 months on VAC . Estimated survival is also similar for the two regimens . Ten of the patients treated with high‐dose CF experienced septic episodes and four died . Toxicity on the CF arm necessitated premature closure of the study , and thus full statistical comparison of the efficacy of the two regimens can not be made Summary From October 1973 to October 1977 the ECOG prospect ively evaluated cyclophosphamide , methotrexate , and fluorouracil ( CMF ) versus CMF plus fluoxymesterone ( CMFH ) maintenance therapies in responders to 6 months of induction therapy which consisted of either CMF , CMF plus prednisone ( CMFP ) , or adriamycin plus vincristine ( AV ) . Following the maintenance r and omization 12 % of the patients converted from a PR to a CR status . The median time from r and omization to treatment failure was 9.5 months for CMFH and 6.7 months for CMF ( p = 0.03 ) . This difference was observed only for partial responders ( p = 0.01 ) and not for complete responders . Patients receiving CMFH  tended to maintain higher hemoglobin , leukocyte , and platelet levels , and receive a higher dosage of each of the cytotoxic drugs . The results are taken as evidence that the addition of fluoxymesterone to a maintenance CMF regimen provides a therapeutic advantage . It is hypothesized that this effect is due at least in part to fluoxymesterone associated maintenance of improved marrow function result ing in greater myelosuppressive drug delivery 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 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 A prospect i ve study with two cytotoxic combinations ( cyclophosphamide , methotrexate , and fluorouracil ( CMF ) , and adriamycin plus vincristine ( AV ) ) was carried out in 110 patients with advanced breast cancer . There was no significant difference between the treatment groups in the response rate after primary treatment , the median duration of response , and the median survival . In both groups responders survived for longer than non-responders . Secondary treatment after crossover for progression or relapse result ed in response rates of 35 % for AV and 20 % for CMF .  Toxicity was mainly represented by reversible haemosuppression . These results are comparable with those obtained with other multiple-drug regimens , and combination chemotherapy alone seems to have reached a plateau in its capacity to control disseminated breast cancer The prospect i ve controlled Phase III clinical trial tested the therapeutic value of the cis-platinum-adriamycin-cyclophosphamide combination ( CAP ) , compared with the combination including cyclophosphamide , methotrexate , 5-fluorouracil , vincristine and prednisolone ( CMFVP ) , in untreated metastatic breast cancer . One hundred and twenty-three patients ( > 2 cycles ) were evaluated : 61 on the CAP , and 62 on the CMFVP schedule .  An objective response ( CR+PR ) to CAP combination chemotherapy was achieved in 72 % of patients ( 43/61 ) , with a high rate ( 36 % ) of complete remissions . In terms of metastatic site , the response rate appeared to be particularly high in soft tissue and visceral organ ( lung , liver ) metastases . In the CMFVP group , an objective response was noted in 26 of 62 patients ( 42 % ) , with 16 % complete remissions . The difference in overall therapeutic response - and in the complete remission rate as well - was statistically significant to the advantage of the CAP regimen ( P < 0.01 ) . The duration of remissions was 6 - 28 + months ( mean = 14 ) for the CAP , and 4 - 15 + months ( mean = 9 ) for the CMFVP schedule . Toxic side effects were more pronounced in the CAP group , particularly myelosuppression , with anemia prevailing . Side effects to CMFVP treatment were moderate . In 39 CMFVP previously treated cases , CAP was administered as second-line treatment , and an objective response was observed in 51 % of cases ( 20/39 ) . Results of this controlled trial showed the advantage of the CAP combination chemotherapy in the treatment of metastatic breast cancer Summary One hundred and sixteen patients with locally advanced or metastatic breast cancer were r and omized to receive CMF ( cyclophosphamide 600 mg m–2 day 1 and 8 i.v . , 5-fluorouracil 600 mg m–2 day 1 and 8 i.v . , , methotrexate 40 mg m–2 day 1 and 8 i.v . , monthly for 6 cycles ) or MM ( methotrexate 30 mg m–2 , mitoxantrone 6.5 mg m–2 , both i.v . day 1 3-weekly for 8 cycles ) as first line treatment with chemotherapy .  Objective responses occurred in 17 patients out of 58 ( 29 % ) who received CMF and nine out of 58 ( 15 % ) who received MM ; 95 % confidence interval for difference in response rates ( –1%–29 % ) , P = 0.07 . No statistically significant differences were seen in overall survival or time to progression between the two regimes although a tendency towards a shorter progression time on the MM regime must be acknowledged . There was , however , significantly reduced haematological toxicity ( P < 0.001 ) and alopecia ( P < 0.001 ) and fewer dose reductions and delays in patients r and omized to MM . No statistically significant differences were seen between the two regimes in terms of quality of life ( QOL ) . However , some association between QOL and toxicity was apparent overall with pooled QOL estimates tending to indicate a worsening in psychological state with increasing maximum toxicity over treatment . Despite the fact that results surrounding response rates and time to progression did not reach statistical significance , their possible compatibility with an improved outcome on CMF treatment must be borne in mind . However , MM is a well-tolerated regimen with fewer side-effects than CMF , which with careful patient management and follow-up , therefore , may merit consideration as a first-line treatment to palliate patients with metastatic breast cancer who are infirm or elderly Identification of important prognostic factors with respect to the patient 's initial response to therapy was made from a set of 25 covariates available on 281 patients with advanced breast cancer . Since the patients studied were all participants in a r and omized clinical trial that involved three different treatment regimens ( repeated weekly treatment of a combination of cyclophosphamide , methotrexate , 5-fluorouracil , vincristine , and prednisone ; intermittent treatment of the same preceding five drugs given in 5-day courses every 4 weeks ; or treatment every 3 weeks with adriamycin as a single agent ) , the effect of these treatments on the selection of important covariates was assessed . Although some evidence indicated that the set of important covariates differed by treatment , the differences were not strong enough to be of practical importance . Non-Caucasian patients did poorly on all regimens with a response rate of only 31 % compared to 62 % for Caucasian patients . The covariates of major prognostic importance for Caucasians were : disease-free interval , liver involvement , and performance status . Ambulatory patients with long disease-free intervals and no liver involvement had the best prognosis . After adjustments were made for these three covariates , the remaining covariates ( such as menopausal status , bone involvement , number of metastatic sites , and duration of metastatic disease ) were not significantly related to response . As reported earlier , the treatment effect was significant , even after adjustments were made for the important covariates BACKGROUND To compare survival between patients with advanced breast cancer ( ABC ) treated with epirubicin/paclitaxel ( Taxol ) or paclitaxel/carboplatin ( Cp ) chemotherapy . PATIENTS AND METHODS From January 1999 to April 2002 , 327 eligible patients with ABC were r and omized to receive either paclitaxel 175 mg/m(2 ) in a 3-h infusion followed by epirubicin ( EPI ) 80 mg/m(2 ) ( group A ) or paclitaxel , as in group A , followed by Cp at an AUC of 6 mg x min/ml ( group B ) every 3 weeks for six cycles . RESULTS After a median follow-up of 23.5 months , median survival was not significantly different between the two groups ( 22.4 months versus 27.8 months , P=0.25 ) , whereas median time to treatment failure was significantly longer in patients treated with paclitaxel/Cp ( 8.1 months in group A versus 10.8 months in group B , P=0.04 ) . Both regimens were well tolerated . In total , 39 patients ( 24 % ) in group A and 46 ( 29 % ) in group B suffered at least one severe side-effect . Quality -of-life assessment and cost analysis did not reveal any significant differences between the two groups . CONCLUSION Our study suggests that the paclitaxel/Cp combination is an effective therapeutic alternative for patients with ABC in which anthracycline administration has the potential of being harmful To evaluate the substitution of methotrexate with doxorubicin ( Dox ) in CMF-(cyclophosphamide , methotrexate , 5-fluorouracil ) containing regimen for advanced breast cancer , 415 postmenopausal patients below the age of 66 years , na 
    Output:
    