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 Paclitaxel has significant antitumor activity in patients with metastaticbreast cancer who have been previously treated with or exposed to anthracycline-containing chemotherapy .  In this prospect i ve r and omized trial , the role of paclitaxel was evaluated in an adjuvant setting to determine its impact on reducing the risk of recurrence in patients with operable breast cancer . EXPERIMENTAL DESIGN Five hundred twenty-four patients were r and omized to be treated either with 4 cycles of paclitaxel followed by 4 cycles of combination therapy with 5-fluorouracil , Adriamycin , and cyclophosphamide ( Pac/FAC ) or with 8 cycles of FAC alone .  Patients with intact primary breast cancer received the initial 4 cycles of paclitaxel or 4 cycles of FAC in a neoadjuvant setting . Planned duration of therapy was the same in all patients . After completion of 8 cycles of chemotherapy , those patients who were > or = 50 years and whose tumors were positive for estrogen receptors received tamoxifen for 5 years . RESULTS Ninety-two patients have had a recurrence after a median follow-up of 60 months with a range of 5 - 89 months . Estimated disease-free survival at 48 months was 0.83 for FAC and 0.86 for Pac/FAC group . The difference between the two groups was not statistically significant ( P = 0.09 ) . The overall estimated hazard ratio for Pac/FAC compared with FAC derived by fitting the Cox regression model and incorporating terms for prognostic factors was 0.66 . CONCLUSION Preliminary results suggest that the addition of paclitaxel to a FAC regimen of adjuvant or neoadjuvant therapy may further reduce the risk of disease recurrence ; however , differences were not statistically significant . At the time of this analysis , there have been 47 deaths . The survival data are too preliminary to permit meaningful evaluation of the impact of paclitaxel on mortality BACKGROUND The aim of the study was to analyse the toxicity and health related quality of life ( HRQoL ) of breast cancer patients treated with FAC ( 5-fluorouracil , doxorubicin , cyclophosphamide ) and TAC ( docetaxel , doxorubicin , cyclophosphamide ) with and without primary prophylactic G-CSF ( PPG ) .  PATIENTS AND METHODS This was a phase III study to compare FAC and TAC as adjuvant treatment of high-risk node-negative breast cancer patients . After the entry of the first 237 patients , the protocol was amended to include PPG in the TAC arm due to the high incidence of febrile neutropenia . A total of 1047 evaluable patients from 49 centres in Spain , two in Pol and and four in Germany were included in the trial .  Side-effects and the scores of the EORTC QLQ-C30 and QLQ BR-23 question naires were compared in the three groups ( FAC , TAC pre-amendment and TAC post-amendment ) . RESULTS The addition of PPG to TAC significantly reduced the incidence of neutropenic fever , grade 2 - 4 anaemia , asthenia , anorexia , nail disorders , stomatitis , myalgia and dysgeusia . Patient QoL decreased during chemotherapy , more with TAC than FAC , but returned to baseline values afterwards . The addition of PPG to TAC significantly reduced the percentage of patients with clinical ly relevant Global Health Status deterioration ( 10 or more points over baseline value ) at the end of chemotherapy ( 64 % versus 46 % , P<0.03 ) . CONCLUSIONS The addition of PPG significantly reduces the incidence of neutropenic fever associated with TAC chemotherapy as well as that of some TAC-induced haematological and extrahaematological side-effects . The HRQoL of patients treated with TAC is worse than that of those treated with FAC but improves with the addition of PPG , particularly in the final part of chemotherapy treatment PURPOSE This study was design ed to determine whether increasing the dose of doxorubicin in or adding paclitaxel to a st and ard adjuvant chemotherapy regimen for breast cancer patients would prolong time to recurrence and survival . PATIENTS AND METHODS After surgical treatment , 3,121 women with operable breast cancer and involved lymph nodes were r and omly assigned to receive a combination of cyclophosphamide ( C ) , 600 mg/m(2 ) , with one of three doses of doxorubicin ( A ) , 60 , 75 , or 90 mg/m(2 ) , for four cycles followed by either no further therapy or four cycles of paclitaxel at 175 mg/m(2 ) . Tamoxifen was given to 94 % of patients with hormone receptor-positive tumors . RESULTS There was no evidence of a  doxorubicin dose effect . At 5 years , disease-free survival was 69 % , 66 % , and 67 % for patients r and omly assigned to 60 , 75 , and 90 mg/m(2 ) , respectively . The hazard reductions from adding paclitaxel to CA were 17 % for recurrence ( adjusted Wald chi(2 ) P = .0023 ; unadjusted Wilcoxon P = .0011 ) and 18 % for death ( adjusted P = .0064 ; unadjusted P = .0098 ) . At 5 years , the disease-free survival ( + /- SE ) was 65 % ( + /- 1 ) and 70 % ( + /- 1 ) , and overall survival was 77 % ( + /- 1 ) and 80 % ( + /- 1 ) after CA alone or CA plus paclitaxel , respectively . The effects of adding paclitaxel were not significantly different in subsets defined by the protocol , but in an unplanned subset analysis , the hazard ratio of CA plus paclitaxel versus CA alone was 0.72 ( 95 % confidence interval , 0.59 to 0.86 ) for those with estrogen receptor-negative tumors and only 0.91 ( 95 % confidence interval , 0.78 to 1.07 ) for patients with estrogen receptor-positive tumors , almost all of whom received adjuvant tamoxifen . The additional toxicity from adding four cycles of paclitaxel was generally modest . CONCLUSION The addition of four cycles of paclitaxel after the completion of a st and ard course of CA improves the disease-free and overall survival of patients with early breast cancer PURPOSE This study was design ed to determine the effect of adding docetaxel ( T ) to preoperative doxorubicin and cyclophosphamide ( AC ) on  breast cancer response rates and disease-free survival ( DFS ) and overall survival ( OS ) . PATIENTS AND METHODS Women with operable breast cancer ( N = 2,411 ) were r and omly assigned to receive preoperative AC followed by surgery , AC followed by T and surgery , or AC followed by surgery and then T. Tamoxifen was initiated concurrently with chemotherapy . Median time on study for 2,404 patients with follow-up was 77.9 months . RESULTS Addition of T to AC did not significantly impact DFS or OS . There were trends toward improved DFS with addition of T. The addition of T reduced the incidence of local recurrences as first events ( P = .0034 ) . Preoperative T , but not postoperative T , significantly improved DFS in patients who had a clinical partial response after AC ( hazard ratio [ HR ] = 0.71 ; 95 % CI , 0.55 to 0.91 ; P = .007 ) . Pathologic complete response , which was doubled by addition of preoperative T , was a significant predictor of OS regardless of treatment ( HR = 0.33 ; 95 % CI , 0.23 to 0.47 ; P < .0001 ) . Pathologic nodal status after chemotherapy was a significant predictor of OS ( P < .0001 ) . CONCLUSION The addition of preoperative or postoperative T after preoperative AC did not significantly affect OS , slightly improved DFS , and decreased the incidence of local recurrences . The sample size of this study was not sufficient to yield significance for the moderate DFS improvement . Concurrent use of tamoxifen may have limited the impact of adding We evaluated the survival benefit , safety , feasibility , and tolerability of dose-dense ( DD ) adjuvant chemotherapy with epirubicin and paclitaxel for women with node-positive primary breast cancer . R and omised patients ( n=216 ) received DD or conventional-schedule ( CS ) chemotherapy . Dose-dense regimen patients ( n=108 ) received epirubicin 90 mg m−2 plus paclitaxel 175 mg m−2 in four 14-day cycles , then cyclophosphamide 600 mg m−2 , methotrexate 40 mg m−2 , and fluorouracil 600 mg m−2 ( CMF 600/40/600 ) in three 14-day cycles , plus filgrastim 5 μg kg day−1 as growth support in every cycle . Conventional-schedule regimen patients ( n=108 ) received epirubicin 90 mg m−2 plus cyclophosphamide 600 mg m−2 in four 21-day cycles , then CMF 600/40/600 in three 21-day cycles , plus filgrastim if required . After a median follow-up of 38.4 months , 71 patients ( 33 % ) relapsed or died : DD , 33 patients ( 15 deaths ) ; CS , 38 patients ( 22 deaths ) . Dose dense showed a trend for improved disease-free survival ( DFS ) and overall survival ( OS ) . Four-year rates of DFS and OS were 64 and 85 % for DD , and 58 and 75 % for CS . All seven cycles were administered to 208 patients ( 96 % ) . Rates of cycle delay , discontinuation , dose reduction , and adverse events were similar in both groups . Dose-dense sequential chemotherapy with epirubicin/paclitaxel then CMF , supported by filgrastim , is safe and improves survival for patients with node-positive breast cancer LBA520 Background : Docetaxel is among the most active drugs for advanced breast cancer and it has recently shown efficacy in the adjuvant setting too . This trial is aim ed at comparing the efficacy and tolerability of a sequential approach of a chemotherapy combination regimen containing docetaxel to a st and ard anthracycline-based regimen as adjuvant therapy in node-positive ( N+ ) early breast cancer . METHODS Between July 1998 and July 2002 , 972 N+ early breast cancer patients were r and omized to either arm A ( E→CMF ) :  Epirubicin ( E ) 120 mg/m2 iv d1 q21 × 4 cycles followed by Cyclophosphamide 600 mg/m2 iv , Methotrexate 40 mg/m2 iv and Fluorouracil 600 mg/m2 iv ( CMF ) d1,8 q28 × 4 cycles ; or armB ( E→T→CMF ) in which Docetaxel 100 mg/m2 iv ( T ) d1 q21 × 4 cycles was administered after the 4th cycle of E and before the 1st cycle of CMF . Treatment allocation was performed by a computer program using a dynamic balancing algorithm . Balancing factors were : center , lymph node involvement ( 1 to 3 , 4 to 9 , > 10 ) , estrogen receptor status ( negative/positive/unknown ) , menopausal status ( pre/post ) . During chemotherapy pts were subjected to physical examination and blood chemistry tests every 3 wks , hematology was repeated weekly . At the completion of treatment pts were followed up every 3 months for the first 2 years , every 6 months for years 3 - 5 and every 12 months for years 6 - 10 . Primary endpoint was disease free survival ( DFS ) and secondary endpoints were tolerability and overall survival ( OS ) . The study was design ed to detect a hazard ratio of 0.70 , assuming an α of 0.05 ( two sided ) , a power of 0.80 and an expected DFS in Arm A of 0.65 at 5 years . This required 480 pts per Arm and 250 events . RESULTS As of March 27th 2006 , 486 pts were enrolled in arm A and 486 in arm B , 252 primary events were recorded and the median follow up was 53 months . DFS at 5 years was 0.67 in arm A vs 0.74 in arm B with an estimated Hazard Ratio ( HR ) of 0.80 ( 95 % CI : 0.62 - 1.03 , p = 0.079 ) . After adjustement by predefined balancing factors ( ER , Nodal and menopausal status ) the HR was 0.78 ( 95 % CIs : 0.61 - 1.00 ; p = 0.05 ) . As for OS , 117 deaths were observed with HR of 0.74 ( 95 % CIs : 0.51 - 1.07 , p = 0.10 ) . CONCLUSIONS Sequential E→T→CMF yields a borderline significant improvement of DFS . Follow up up date is still ongoing . [ Table : see text ] BACKGRO 
    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 Paclitaxel has significant antitumor activity in patients with metastaticbreast cancer who have been previously treated with or exposed to anthracycline-containing chemotherapy .  In this prospect i ve r and omized trial , the role of paclitaxel was evaluated in an adjuvant setting to determine its impact on reducing the risk of recurrence in patients with operable breast cancer . EXPERIMENTAL DESIGN Five hundred twenty-four patients were r and omized to be treated either with 4 cycles of paclitaxel followed by 4 cycles of combination therapy with 5-fluorouracil , Adriamycin , and cyclophosphamide ( Pac/FAC ) or with 8 cycles of FAC alone .  Patients with intact primary breast cancer received the initial 4 cycles of paclitaxel or 4 cycles of FAC in a neoadjuvant setting . Planned duration of therapy was the same in all patients . After completion of 8 cycles of chemotherapy , those patients who were > or = 50 years and whose tumors were positive for estrogen receptors received tamoxifen for 5 years . RESULTS Ninety-two patients have had a recurrence after a median follow-up of 60 months with a range of 5 - 89 months . Estimated disease-free survival at 48 months was 0.83 for FAC and 0.86 for Pac/FAC group . The difference between the two groups was not statistically significant ( P = 0.09 ) . The overall estimated hazard ratio for Pac/FAC compared with FAC derived by fitting the Cox regression model and incorporating terms for prognostic factors was 0.66 . CONCLUSION Preliminary results suggest that the addition of paclitaxel to a FAC regimen of adjuvant or neoadjuvant therapy may further reduce the risk of disease recurrence ; however , differences were not statistically significant . At the time of this analysis , there have been 47 deaths . The survival data are too preliminary to permit meaningful evaluation of the impact of paclitaxel on mortality BACKGROUND The aim of the study was to analyse the toxicity and health related quality of life ( HRQoL ) of breast cancer patients treated with FAC ( 5-fluorouracil , doxorubicin , cyclophosphamide ) and TAC ( docetaxel , doxorubicin , cyclophosphamide ) with and without primary prophylactic G-CSF ( PPG ) .  PATIENTS AND METHODS This was a phase III study to compare FAC and TAC as adjuvant treatment of high-risk node-negative breast cancer patients . After the entry of the first 237 patients , the protocol was amended to include PPG in the TAC arm due to the high incidence of febrile neutropenia . A total of 1047 evaluable patients from 49 centres in Spain , two in Pol and and four in Germany were included in the trial .  Side-effects and the scores of the EORTC QLQ-C30 and QLQ BR-23 question naires were compared in the three groups ( FAC , TAC pre-amendment and TAC post-amendment ) . RESULTS The addition of PPG to TAC significantly reduced the incidence of neutropenic fever , grade 2 - 4 anaemia , asthenia , anorexia , nail disorders , stomatitis , myalgia and dysgeusia . Patient QoL decreased during chemotherapy , more with TAC than FAC , but returned to baseline values afterwards . The addition of PPG to TAC significantly reduced the percentage of patients with clinical ly relevant Global Health Status deterioration ( 10 or more points over baseline value ) at the end of chemotherapy ( 64 % versus 46 % , P<0.03 ) . CONCLUSIONS The addition of PPG significantly reduces the incidence of neutropenic fever associated with TAC chemotherapy as well as that of some TAC-induced haematological and extrahaematological side-effects . The HRQoL of patients treated with TAC is worse than that of those treated with FAC but improves with the addition of PPG , particularly in the final part of chemotherapy treatment PURPOSE This study was design ed to determine whether increasing the dose of doxorubicin in or adding paclitaxel to a st and ard adjuvant chemotherapy regimen for breast cancer patients would prolong time to recurrence and survival . PATIENTS AND METHODS After surgical treatment , 3,121 women with operable breast cancer and involved lymph nodes were r and omly assigned to receive a combination of cyclophosphamide ( C ) , 600 mg/m(2 ) , with one of three doses of doxorubicin ( A ) , 60 , 75 , or 90 mg/m(2 ) , for four cycles followed by either no further therapy or four cycles of paclitaxel at 175 mg/m(2 ) . Tamoxifen was given to 94 % of patients with hormone receptor-positive tumors . RESULTS There was no evidence of a  doxorubicin dose effect . At 5 years , disease-free survival was 69 % , 66 % , and 67 % for patients r and omly assigned to 60 , 75 , and 90 mg/m(2 ) , respectively . The hazard reductions from adding paclitaxel to CA were 17 % for recurrence ( adjusted Wald chi(2 ) P = .0023 ; unadjusted Wilcoxon P = .0011 ) and 18 % for death ( adjusted P = .0064 ; unadjusted P = .0098 ) . At 5 years , the disease-free survival ( + /- SE ) was 65 % ( + /- 1 ) and 70 % ( + /- 1 ) , and overall survival was 77 % ( + /- 1 ) and 80 % ( + /- 1 ) after CA alone or CA plus paclitaxel , respectively . The effects of adding paclitaxel were not significantly different in subsets defined by the protocol , but in an unplanned subset analysis , the hazard ratio of CA plus paclitaxel versus CA alone was 0.72 ( 95 % confidence interval , 0.59 to 0.86 ) for those with estrogen receptor-negative tumors and only 0.91 ( 95 % confidence interval , 0.78 to 1.07 ) for patients with estrogen receptor-positive tumors , almost all of whom received adjuvant tamoxifen . The additional toxicity from adding four cycles of paclitaxel was generally modest . CONCLUSION The addition of four cycles of paclitaxel after the completion of a st and ard course of CA improves the disease-free and overall survival of patients with early breast cancer PURPOSE This study was design ed to determine the effect of adding docetaxel ( T ) to preoperative doxorubicin and cyclophosphamide ( AC ) on  breast cancer response rates and disease-free survival ( DFS ) and overall survival ( OS ) . PATIENTS AND METHODS Women with operable breast cancer ( N = 2,411 ) were r and omly assigned to receive preoperative AC followed by surgery , AC followed by T and surgery , or AC followed by surgery and then T. Tamoxifen was initiated concurrently with chemotherapy . Median time on study for 2,404 patients with follow-up was 77.9 months . RESULTS Addition of T to AC did not significantly impact DFS or OS . There were trends toward improved DFS with addition of T. The addition of T reduced the incidence of local recurrences as first events ( P = .0034 ) . Preoperative T , but not postoperative T , significantly improved DFS in patients who had a clinical partial response after AC ( hazard ratio [ HR ] = 0.71 ; 95 % CI , 0.55 to 0.91 ; P = .007 ) . Pathologic complete response , which was doubled by addition of preoperative T , was a significant predictor of OS regardless of treatment ( HR = 0.33 ; 95 % CI , 0.23 to 0.47 ; P < .0001 ) . Pathologic nodal status after chemotherapy was a significant predictor of OS ( P < .0001 ) . CONCLUSION The addition of preoperative or postoperative T after preoperative AC did not significantly affect OS , slightly improved DFS , and decreased the incidence of local recurrences . The sample size of this study was not sufficient to yield significance for the moderate DFS improvement . Concurrent use of tamoxifen may have limited the impact of adding We evaluated the survival benefit , safety , feasibility , and tolerability of dose-dense ( DD ) adjuvant chemotherapy with epirubicin and paclitaxel for women with node-positive primary breast cancer . R and omised patients ( n=216 ) received DD or conventional-schedule ( CS ) chemotherapy . Dose-dense regimen patients ( n=108 ) received epirubicin 90 mg m−2 plus paclitaxel 175 mg m−2 in four 14-day cycles , then cyclophosphamide 600 mg m−2 , methotrexate 40 mg m−2 , and fluorouracil 600 mg m−2 ( CMF 600/40/600 ) in three 14-day cycles , plus filgrastim 5 μg kg day−1 as growth support in every cycle . Conventional-schedule regimen patients ( n=108 ) received epirubicin 90 mg m−2 plus cyclophosphamide 600 mg m−2 in four 21-day cycles , then CMF 600/40/600 in three 21-day cycles , plus filgrastim if required . After a median follow-up of 38.4 months , 71 patients ( 33 % ) relapsed or died : DD , 33 patients ( 15 deaths ) ; CS , 38 patients ( 22 deaths ) . Dose dense showed a trend for improved disease-free survival ( DFS ) and overall survival ( OS ) . Four-year rates of DFS and OS were 64 and 85 % for DD , and 58 and 75 % for CS . All seven cycles were administered to 208 patients ( 96 % ) . Rates of cycle delay , discontinuation , dose reduction , and adverse events were similar in both groups . Dose-dense sequential chemotherapy with epirubicin/paclitaxel then CMF , supported by filgrastim , is safe and improves survival for patients with node-positive breast cancer LBA520 Background : Docetaxel is among the most active drugs for advanced breast cancer and it has recently shown efficacy in the adjuvant setting too . This trial is aim ed at comparing the efficacy and tolerability of a sequential approach of a chemotherapy combination regimen containing docetaxel to a st and ard anthracycline-based regimen as adjuvant therapy in node-positive ( N+ ) early breast cancer . METHODS Between July 1998 and July 2002 , 972 N+ early breast cancer patients were r and omized to either arm A ( E→CMF ) :  Epirubicin ( E ) 120 mg/m2 iv d1 q21 × 4 cycles followed by Cyclophosphamide 600 mg/m2 iv , Methotrexate 40 mg/m2 iv and Fluorouracil 600 mg/m2 iv ( CMF ) d1,8 q28 × 4 cycles ; or armB ( E→T→CMF ) in which Docetaxel 100 mg/m2 iv ( T ) d1 q21 × 4 cycles was administered after the 4th cycle of E and before the 1st cycle of CMF . Treatment allocation was performed by a computer program using a dynamic balancing algorithm . Balancing factors were : center , lymph node involvement ( 1 to 3 , 4 to 9 , > 10 ) , estrogen receptor status ( negative/positive/unknown ) , menopausal status ( pre/post ) . During chemotherapy pts were subjected to physical examination and blood chemistry tests every 3 wks , hematology was repeated weekly . At the completion of treatment pts were followed up every 3 months for the first 2 years , every 6 months for years 3 - 5 and every 12 months for years 6 - 10 . Primary endpoint was disease free survival ( DFS ) and secondary endpoints were tolerability and overall survival ( OS ) . The study was design ed to detect a hazard ratio of 0.70 , assuming an α of 0.05 ( two sided ) , a power of 0.80 and an expected DFS in Arm A of 0.65 at 5 years . This required 480 pts per Arm and 250 events . RESULTS As of March 27th 2006 , 486 pts were enrolled in arm A and 486 in arm B , 252 primary events were recorded and the median follow up was 53 months . DFS at 5 years was 0.67 in arm A vs 0.74 in arm B with an estimated Hazard Ratio ( HR ) of 0.80 ( 95 % CI : 0.62 - 1.03 , p = 0.079 ) . After adjustement by predefined balancing factors ( ER , Nodal and menopausal status ) the HR was 0.78 ( 95 % CIs : 0.61 - 1.00 ; p = 0.05 ) . As for OS , 117 deaths were observed with HR of 0.74 ( 95 % CIs : 0.51 - 1.07 , p = 0.10 ) . CONCLUSIONS Sequential E→T→CMF yields a borderline significant improvement of DFS . Follow up up date is still ongoing . [ Table : see text ] BACKGRO 
    Output:
    