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: 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 The aim of the study was to compare our reference adjuvant chemotherapy , FEC100 ( fluorouracil 500 mg m−2 , epirubicin 100 mg m−2 and cyclophosphamide 500 mg m−2 , six cycles every 21 days ) , to an epirubicin – vinorelbine ( Epi-Vnr ) combination for early , poor-prognosis breast cancer patients . Patients ( 482 ) were r and omised to receive FEC100 , or Epi-Vnr ( epirubicin 50 mg m−2 day 1 and vinorelbine 25 mg m−2 , days 1 and 8 , six cycles every 21 days ) . The 7-year disease-free survival rates were 59.4 and 58.8 % , respectively ( P=0.47 ) . The relative dose intensity of planned epirubicin doses was 89.1 % with FEC100 and 88.9 % with Epi-Vnr . There were significantly more grade s 3–4 neutropenia ( P=0.009 ) with Epi-Vnr , and significantly more nausea-vomiting ( P<0.0001 ) , stomatitis ( P=0.0007 ) and alopecia ( P<0.0001 ) with FEC100 . No cases of congestive heart failure were reported , whereas four decreases in left ventricular ejection fraction occurred after FEC100 and five after Epi-Vnr . One case of acute myeloblastic leukaemia was registered in the FEC100 arm . After 7 years of follow-up , there was no difference between treatment arms . Epi-Vnr regimen provided a good efficacy in such poor-prognosis breast cancer patients , and could be an alternative to FEC100 , taking into account respective safety profiles of both regimens PURPOSE We previously reported that four cycles of docetaxel/cyclophosphamide ( TC ) produced superior disease-free survival ( DFS ) compared with four cycles of doxorubicin/cyclophosphamide ( AC ) in early breast cancer . Older women are under-represented in adjuvant chemotherapy trials . In our trial 16 % of patients were > or = 65 years . We now report 7-year results for DFS and overall survival ( OS ) as well as the impact of age , hormone receptor status , and HER2 status on outcome and toxicity . PATIENTS AND METHODS Patients were r and omly assigned to receive either four cycles of st and ard-dose AC ( 60/600 mg/m(2 ) ; n = 510 ) , or TC ( 75/600 mg/m(2 ) ; n = 506 ) , administered by intravenous infusion every 3 weeks . RESULTS The median age in women younger than 65 , was 50 years ( range , 27 to 64 ) and for women > or = 65 was 69 years ( range , 65 to 77 ) . Baseline characteristics in the two age subgroups were generally well matched , except that older women tended to have more lymph node involvement . At a median of 7 years follow-up , the difference in DFS between TC and AC was significant ( 81 % TC v 75 % AC ; P = .033 ; hazard ratio [ HR ] , 0.74 ; 95 % CI 0.56 to 0.98 ) as was OS ( 87 % TC v 82 % AC ; P = .032 ; HR , 0.69 ; 95 % CI , 0.50 to 0.97 ) . TC was superior in older patients as well as younger patients . There was no interaction of hormone-receptor status or HER-2 status and treatment . Older women experienced more febrile neutropenia with TC and more anemia with AC . CONCLUSION With longer follow-up , four cycles of TC was superior to st and ard AC ( DFS and OS ) and was a tolerable regimen in both older and younger patients 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 BACKGROUND TAC ( docetaxel/doxorubicin/cyclophosphamide ) is associated with high incidences of grade 4 neutropenia and febrile neutropenia ( FN ) . This analysis compared the efficacies of four regimens for primary prophylaxis of FN and related toxic effects in breast cancer patients receiving neoadjuvant TAC . PATIENTS AND METHODS Patients with stage T2-T4 primary breast cancer were scheduled to receive 6 - 8 cycles of TAC .  Primary prophylaxis was : ciprofloxacin 500 mg orally twice daily on days 5 - 14 ( n = 253 patients ; 1478 cycles ) , daily granulocyte colony-stimulating factor ( G-CSF ) ( filgrastim 5 microg/kg/day or lenograstim 150 microg/m(2)/day ) on days 5 - 10 ( n = 377 ; 2400 cycles ) , pegfilgrastim 6 mg on day 2 ( n = 305 ; 1930 cycles ) , or pegfilgrastim plus ciprofloxacin ( n = 321 ; 1890 cycles ) . RESULTS Pegfilgrastim with/without ciprofloxacin was significantly more effective than daily G-CSF or ciprofloxacin in preventing FN ( 5 % and 7 % versus 18 % and 22 % of patients ; all P < 0.001 ) , grade 4 neutropenia , and leukopenia .  Pegfilgrastim plus ciprofloxacin completely prevented first cycle FN ( P < 0.01 versus pegfilgrastim alone ) and fatal neutropenic events . CONCLUSION Ciprofloxacin alone , or daily G-CSF from day 5 - 10 ( as in common practice ) , provided suboptimal protection against FN and related toxic effects in patients receiving TAC . Pegfilgrastim was significantly more effective in this setting , especially if given with ciprofloxacin BACKGROUND To compare the efficacy of continuous infusional 5-fluorouracil (5-FU)-based chemotherapy against conventional bolus chemotherapy in the preoperative treatment of patients with large operable early breast cancer . PATIENTS AND METHODS Four hundred and twenty-six women with histologically proven 3 cm invasive early breast cancer were r and omised to receive pre-operative infusional 5-FU 200 mg/m(2 ) by daily 24 h continuous infusion via a Hickman line for 18 weeks with epirubicin 60 mg/m(2 ) intravenous ( i.v . ) bolus on day 1 and cisplatin 60 mg/m(2 ) i.v . bolus on day 1 , both repeating 3-weekly ( infusional ECisF ) , or conventional bolus doxorubicin 60 mg/m(2 ) i.v . on day 1 and cyclophosphamide 600 mg/m(2 ) i.v . on day 1 , both repeating 3-weekly ( AC ) , both schedules for six courses . Patients subsequently had local therapy ( surgery or radiotherapy or both ) and tamoxifen 20 mg orally daily as appropriate . RESULTS The 5 year results for AC and infusional ECisF , respectively , were as follows : overall response , 75 % and 77 % ; complete clinical remission , 31 % and 34 % ; pathological complete remission ( pathCR ) , 16 % for both ; and pathCR with residual ductal carcinoma in situ ( DCIS ) , 25 % and 24 % . Mastectomy rates were 37 % and 34 % , respectively . Five-year overall survival was 74 % for AC and 82 % for infusional ECisF ( hazard ratio 0.76 , 95 % confidence interval 0.51 - 1.13 ; P = 0.18 ) . Both treatments were well tolerated . Grade III/IV lethargy , vomiting , alopecia and plantar-palmar erythema were significantly greater for infusional ECisF ; grade III/IV leucopenia was significantly greater for AC . CONCLUSIONS Preoperative continuous infusional 5-FU-based chemotherapy is no more active than conventional AC for early breast cancer ; with a median 5 year follow-up , the infusion-based schedule shows a non-significant trend towards improved survival In a study of the effectiveness of high intravenous doses of metoclopramide as an antiemetic , 41 patients with advanced cancer who were being treated with cisplatin  were entered into two double-blind trials . In the first trial patients were r and omly assigned to receive either metoclopramide or placebo , and in the second trial they received either metoclopramide or prochlorperazine . Patients given metoclopramide had significantly fewer episodes of emesis than patients given placebo ( medians , 1.0 vs. 10.5 ; P = 0.001 ) or prochlorperazine ( medians , 1.5 vs. 12.0 ; P = 0.005 ) . Metoclopramide was superior to placebo and to prochlorperazine in reducing the volume of emesis ( P = 0.001 and P = 0.022 , respectively ) and was more effective than placebo in shortening the duration of nausea ( P = 0.042 ) and vomiting ( P = 0.028 ) . Side effects from metoclopramide were minor , with m 
    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: 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 The aim of the study was to compare our reference adjuvant chemotherapy , FEC100 ( fluorouracil 500 mg m−2 , epirubicin 100 mg m−2 and cyclophosphamide 500 mg m−2 , six cycles every 21 days ) , to an epirubicin – vinorelbine ( Epi-Vnr ) combination for early , poor-prognosis breast cancer patients . Patients ( 482 ) were r and omised to receive FEC100 , or Epi-Vnr ( epirubicin 50 mg m−2 day 1 and vinorelbine 25 mg m−2 , days 1 and 8 , six cycles every 21 days ) . The 7-year disease-free survival rates were 59.4 and 58.8 % , respectively ( P=0.47 ) . The relative dose intensity of planned epirubicin doses was 89.1 % with FEC100 and 88.9 % with Epi-Vnr . There were significantly more grade s 3–4 neutropenia ( P=0.009 ) with Epi-Vnr , and significantly more nausea-vomiting ( P<0.0001 ) , stomatitis ( P=0.0007 ) and alopecia ( P<0.0001 ) with FEC100 . No cases of congestive heart failure were reported , whereas four decreases in left ventricular ejection fraction occurred after FEC100 and five after Epi-Vnr . One case of acute myeloblastic leukaemia was registered in the FEC100 arm . After 7 years of follow-up , there was no difference between treatment arms . Epi-Vnr regimen provided a good efficacy in such poor-prognosis breast cancer patients , and could be an alternative to FEC100 , taking into account respective safety profiles of both regimens PURPOSE We previously reported that four cycles of docetaxel/cyclophosphamide ( TC ) produced superior disease-free survival ( DFS ) compared with four cycles of doxorubicin/cyclophosphamide ( AC ) in early breast cancer . Older women are under-represented in adjuvant chemotherapy trials . In our trial 16 % of patients were > or = 65 years . We now report 7-year results for DFS and overall survival ( OS ) as well as the impact of age , hormone receptor status , and HER2 status on outcome and toxicity . PATIENTS AND METHODS Patients were r and omly assigned to receive either four cycles of st and ard-dose AC ( 60/600 mg/m(2 ) ; n = 510 ) , or TC ( 75/600 mg/m(2 ) ; n = 506 ) , administered by intravenous infusion every 3 weeks . RESULTS The median age in women younger than 65 , was 50 years ( range , 27 to 64 ) and for women > or = 65 was 69 years ( range , 65 to 77 ) . Baseline characteristics in the two age subgroups were generally well matched , except that older women tended to have more lymph node involvement . At a median of 7 years follow-up , the difference in DFS between TC and AC was significant ( 81 % TC v 75 % AC ; P = .033 ; hazard ratio [ HR ] , 0.74 ; 95 % CI 0.56 to 0.98 ) as was OS ( 87 % TC v 82 % AC ; P = .032 ; HR , 0.69 ; 95 % CI , 0.50 to 0.97 ) . TC was superior in older patients as well as younger patients . There was no interaction of hormone-receptor status or HER-2 status and treatment . Older women experienced more febrile neutropenia with TC and more anemia with AC . CONCLUSION With longer follow-up , four cycles of TC was superior to st and ard AC ( DFS and OS ) and was a tolerable regimen in both older and younger patients 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 BACKGROUND TAC ( docetaxel/doxorubicin/cyclophosphamide ) is associated with high incidences of grade 4 neutropenia and febrile neutropenia ( FN ) . This analysis compared the efficacies of four regimens for primary prophylaxis of FN and related toxic effects in breast cancer patients receiving neoadjuvant TAC . PATIENTS AND METHODS Patients with stage T2-T4 primary breast cancer were scheduled to receive 6 - 8 cycles of TAC .  Primary prophylaxis was : ciprofloxacin 500 mg orally twice daily on days 5 - 14 ( n = 253 patients ; 1478 cycles ) , daily granulocyte colony-stimulating factor ( G-CSF ) ( filgrastim 5 microg/kg/day or lenograstim 150 microg/m(2)/day ) on days 5 - 10 ( n = 377 ; 2400 cycles ) , pegfilgrastim 6 mg on day 2 ( n = 305 ; 1930 cycles ) , or pegfilgrastim plus ciprofloxacin ( n = 321 ; 1890 cycles ) . RESULTS Pegfilgrastim with/without ciprofloxacin was significantly more effective than daily G-CSF or ciprofloxacin in preventing FN ( 5 % and 7 % versus 18 % and 22 % of patients ; all P < 0.001 ) , grade 4 neutropenia , and leukopenia .  Pegfilgrastim plus ciprofloxacin completely prevented first cycle FN ( P < 0.01 versus pegfilgrastim alone ) and fatal neutropenic events . CONCLUSION Ciprofloxacin alone , or daily G-CSF from day 5 - 10 ( as in common practice ) , provided suboptimal protection against FN and related toxic effects in patients receiving TAC . Pegfilgrastim was significantly more effective in this setting , especially if given with ciprofloxacin BACKGROUND To compare the efficacy of continuous infusional 5-fluorouracil (5-FU)-based chemotherapy against conventional bolus chemotherapy in the preoperative treatment of patients with large operable early breast cancer . PATIENTS AND METHODS Four hundred and twenty-six women with histologically proven 3 cm invasive early breast cancer were r and omised to receive pre-operative infusional 5-FU 200 mg/m(2 ) by daily 24 h continuous infusion via a Hickman line for 18 weeks with epirubicin 60 mg/m(2 ) intravenous ( i.v . ) bolus on day 1 and cisplatin 60 mg/m(2 ) i.v . bolus on day 1 , both repeating 3-weekly ( infusional ECisF ) , or conventional bolus doxorubicin 60 mg/m(2 ) i.v . on day 1 and cyclophosphamide 600 mg/m(2 ) i.v . on day 1 , both repeating 3-weekly ( AC ) , both schedules for six courses . Patients subsequently had local therapy ( surgery or radiotherapy or both ) and tamoxifen 20 mg orally daily as appropriate . RESULTS The 5 year results for AC and infusional ECisF , respectively , were as follows : overall response , 75 % and 77 % ; complete clinical remission , 31 % and 34 % ; pathological complete remission ( pathCR ) , 16 % for both ; and pathCR with residual ductal carcinoma in situ ( DCIS ) , 25 % and 24 % . Mastectomy rates were 37 % and 34 % , respectively . Five-year overall survival was 74 % for AC and 82 % for infusional ECisF ( hazard ratio 0.76 , 95 % confidence interval 0.51 - 1.13 ; P = 0.18 ) . Both treatments were well tolerated . Grade III/IV lethargy , vomiting , alopecia and plantar-palmar erythema were significantly greater for infusional ECisF ; grade III/IV leucopenia was significantly greater for AC . CONCLUSIONS Preoperative continuous infusional 5-FU-based chemotherapy is no more active than conventional AC for early breast cancer ; with a median 5 year follow-up , the infusion-based schedule shows a non-significant trend towards improved survival In a study of the effectiveness of high intravenous doses of metoclopramide as an antiemetic , 41 patients with advanced cancer who were being treated with cisplatin  were entered into two double-blind trials . In the first trial patients were r and omly assigned to receive either metoclopramide or placebo , and in the second trial they received either metoclopramide or prochlorperazine . Patients given metoclopramide had significantly fewer episodes of emesis than patients given placebo ( medians , 1.0 vs. 10.5 ; P = 0.001 ) or prochlorperazine ( medians , 1.5 vs. 12.0 ; P = 0.005 ) . Metoclopramide was superior to placebo and to prochlorperazine in reducing the volume of emesis ( P = 0.001 and P = 0.022 , respectively ) and was more effective than placebo in shortening the duration of nausea ( P = 0.042 ) and vomiting ( P = 0.028 ) . Side effects from metoclopramide were minor , with m 
    Output:
    