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 activity and toxicity of single-agent st and ard-dose doxorubicin were compared with that of two schedules of high-dose epirubicin . A total of 334 chemonaive patients with histologically confirmed advanced soft-tissue sarcomas received ( A ) doxorubicin 75 mg m(-2 ) on day 1 ( 112 patients ) , ( B ) epirubicin 150 mg m(-2 ) on day 1 ( 111 patients ) or ( C ) epirubicin 50 mg m(-2 ) day(-1 ) on days 1 , 2 and 3 ( 111 patients ) ; all given as bolus injection at 3-week intervals . A median of four treatment cycles was given . Median age was 52 years ( 19 - 70 years ) and performance score 1 ( 0 - 2 ) . Of 314 evaluable patients , 45 ( 14 % ) had an objective tumour response  ( eight complete response , 35 partial response ) . There were no differences among the three groups . Median time to progression for groups A , B and C was 16 , 14 and 12 weeks , and median survival 45 , 47 and 45 weeks respectively . Neither progression-free ( P = 0.93 ) nor overall survival ( P = 0.89 ) differed among the three groups . After the first cycle of therapy , two patients died of infection and one owing to cardiovascular disease , all on epirubicin . Both dose schedules of epirubicin were more myelotoxic than doxorubicin .  Cardiotoxicity ( > or = grade 3 ) occurred in 1 % , 0 % and 2 % respectively . Regardless of the schedule , high-dose epirubicin is not a preferred alternative to st and ard-dose doxorubicin in the treatment of patients with advanced soft-tissue sarcomas Eighty-three patients with advanced soft tissue sarcoma who had received no prior chemotherapy entered a r and omised phase II study comparing carminomycin ( CMM ) 20 mg/m2 with adriamycin ( ADM ) 75 mg/m2 , both administered i.v . bolus every 3 weeks . Six patients were ineligible and response could not be evaluated in 6 additional patients . Thirty-eight evaluable patients received ADM and 33 received CMM . There was one complete response to ADM and 10 partial responses , an overall response rate of 29 % . CMM showed significantly ( P = 0.01 ) lower antitumour activity -- one partial response ( 3 % ) . Stabilisation of disease was similar in both arms ( 47 and 45 % ) , but fewer patients progressed on ADM ( 24 compared to 52 % ) . Duration s of response dating from the start of chemotherapy were 5 months for complete remission on ADM , a median of 7 months ( range 4 - 17 ) for partial response on ADM and 14 months for the one partial remission on CMM . Although the median time to progression for all patients receiving CMM ( 2 months ) was significantly ( P = 0.001 ) shorter than for those receiving ADM ( 5 months ) , patients on ADM had only a marginally significant longer duration of survival ( P = 0.06 ) than the patients receiving CMM . A leucocyte nadir less than 2.0 X 10(9)/l occurred in 38 % of patients receiving ADM and 43 % receiving CMM .  Anaemia and thrombocytopoenia were uncommon . Other toxicities such as nausea , vomiting , anorexia and alopecia were more severe in the ADM group . There was one infective death secondary to leucopoenia in the ADM arm , and one patient who had received 109 mg/m2 CMM + 255 mg/m2 ADM developed progressively fatal cardiomyopathy PURPOSE The aim of this trial was to compare the activity and toxicity of single-agent doxorubicin with that of two multidrug regimens in the treatment of patients with adult advanced soft tissue sarcomas . PATIENTS AND METHODS This was a prospect i ve r and omized phase III trial performed by 35 cancer centers within the Soft Tissue and Bone Sarcoma Group of the European Organization for Research and Treatment of Cancer ( EORTC ) . Six hundred sixty-three eligible patients were r and omly allocated to receive either doxorubicin 75 mg/m2 ( arm A ) , cyclophosphamide , vincristine , doxorubicin , and dacarbazine ( CYVADIC ) ( arm B ) , or ifosfamide 5 g/m2 plus doxorubicin 50 mg/m2 ( arm C ) . RESULTS The overall response rate was 24 % ( 95 % confidence interval , 20.7 % to 27.3 % ) among eligible patients and 26 % among assessable patients . No statistically significant difference was detected among the three study arms in terms of response rate ( arm A , 23.3 % ; arm B , 28.4 % ; and arm C , 28.1 % ) , remission duration ( median , 46 weeks on arm A , 48 weeks on arm B , and 44 weeks on arm C ) , or overall survival ( median , 52 weeks on arm A , 51 weeks on arm B , and 55 weeks on arm C ) . The degree of myelosuppression was significantly greater for the combination of ifosfamide and doxorubicin than for the other two regimens . Cardiotoxicity was also more frequent in this arm , but other toxicities were similar . CONCLUSION In advanced soft tissue sarcomas of adults , single-agent doxorubicin is still the st and ard chemotherapy against which more intensive or new drug treatments should be compared . Combination chemotherapy can not be recommended outside a controlled clinical trial with the exclusion of some subsets of sarcoma patients for whom significant tumor volume reduction may be an important end point of a chemotherapy regimen Ifosfamide ( IFOS ) 5 g/m2 and its parent analog Cyclophosphamide ( CYCLO ) 1.5 g/m2 were studied in a r and omized phase II study , accruing 171 patients with advanced soft tissue sarcoma . Both drugs were administered as 24 hr infusions , every 3 weeks , with comcomitant Mesna 400 mg/m2 i.v . bolus 4 hourly X 9 doses . Twenty-four patients were ineligible and 12 were not evaluable . The groups were well matched for age , previous chemotherapy ( 42 % of the total ) or radiotherapy , the presence of distant metastases and performance status , but there were more females ( 59 % vs. 45 % ) in the IFOS arm . Among the 68 evaluable patients receiving IFOS , there were 2 CR , 10 PR ( overall response 18 % ) , 27 SD and 29 PD . For CYCLO , the corresponding results in 67 patients were 1 CR , 4 PR ( overall response 8 % ) , 23 SD and 39 PD . Using the chi-square test the P values for response rate and linear trend were 0.13 and 0.04 respectively . Response rates were higher for females ( 20 % vs. 5 % , P = 0.01 ) and patients who had not received previous chemotherapy ( 19 % vs. 4 % , P = 0.01 ) . Fourteen of the 17 responses came from a group of 43 females , who had not received previous chemotherapy , for whom the overall response rate was 37.5 % . Remissions were noted in only 4 histological subtypes ( central ly review ed material ) , i.e. , 5 of 17 synovial sarcomas , 7 of 13 mixed mesodermal sarcomas and 2 of 7 fibrosarcomas . One of the 31 leiomyosarcomas responded to Cyclophosphamide .  Duration s of response did not differ significantly between the 2 arms -- median 26 , range 10 - 81 + weeks . Leucopenia was significantly more severe on CYCLO , particularly in patients who had received previous chemotherapy ( P = 0.007 ) . Serious infections occurred in approx . 7 % of patients with no difference between the two drugs , although there was one toxic death on CYCLO .  Nausea and vomiting were significantly worse on  IFOS  and alopecia , related in extent to dose , was seen in both arms . Other side-effects , such as hematuria or rises in serum creatinine and encephalopathy , were infrequent and mild . A higher response rate with less myelosuppression suggests that IFOS may have advantages over CYCLO in combination therapy Recurrent or metastatic uterine sarcoma represents an ominous and aggressive form of malignant disease . In an attempt to define a beneficial treatment program , we compared treatment with doxorubicin ( A ) 60 mg/m2 versus a combination of doxorubicin 60 mg/m2 and cyclophosphamide 500 mg/m ( CA ) , each regimen given every 3 weeks . Of 132 patients entered on study , 104 were eligible ; 50 received A and 54 CA . Pretreatment characteristics were similar , and no patient had received prior chemotherapy . The proportion of complete responses ( CR ) + partial responses ( PR ) for measurable disease patients was 5 of 26 ( 19 % ) for both A and CA . Multivariate analysis done on progression‐free interval ( PFI ) and survival ( S ) showed CA to be of no benefit over A ( PFI , P = 0.22 ; S , P = 0.55 ) . For both A and CA patients , measurable disease ( PFI , P = 0.002 ; S , P = 0.02 , respectively ) , performance status ( PFI , P = 0.004 ; S , P = 0.0002 ; respectively ) , and sites of residual disease ( PFI , P = 0.008 ; S , P = 0.003 , respectively ) were detected as prognostic variables . Conversely , histologic type , age , and recurrence status ( primary versus recurrent at entry ) were not prognostic indicators . These data indicate no significant benefit of CA versus A alone in patients with uterine sarcoma Forty-four of 50 adult patients with advanced soft-tissue sarcoma who had received previous chemotherapy  were evaluable for response after treatment with DTIC . The therapeutic schedule consisted of DTIC 1.2 g/m2 infused over 20 minutes , and repeated every 3 weeks . There were 1 complete and 7 partial remissions ( objective activity 18 % , 95 % C.I. 7%-29 % ) , with a median duration of 8 weeks ( range 5 - 19 ) , with the complete remission lasting 1 yr . Hematologic toxicity was dose-limiting ; W.H.O. greater than or equal to 3 values were observed for WBC in 36 % , and for platelets in 26 % of patients . The non-hematologic toxicity included nausea and vomiting ( 90 % ) , a flu-like syndrome ( 49 % ) , diarrhea ( 35 % ) , pain in the infused vein ( 28 % ) and hypotensive episodes ( 4 % ) . Intermittent high-dose DTIC is active in advanced soft-tissue sarcoma and should be considered for inclusion in combination regimens In a prospect ively r and omized study , 17 evaluable patients treated with adriamycin alone , 60 mg/m2 intravenously every 3 wk , were compared with 14 patients treated with adriamycin in the same dose and schedule plus streptozotocin , 500 mg/m2/day intravenously for 5 days every 3 wk . All patients had advanced sarcomas , but none had previously received either adriamycin or streptozotocin .  Objective responses were seen in 9 patients on the single drug arm ( 4 with more than 50 % tumor shrinkage and 5 with stabilization of disease ) , and in 8 patients given the combination drug arm ( 2 with more than 50 % tumor shrinkage and 6 with stabilization oldisease ) . Duration of response and survivalfrom treatmentfor both treatment groups were similar . Transient hepatic dysfunction , renal function abnormalities , and nausea with vomiting were additive in the combination drug arm , the last two limiting therapy most . Leukopenia , thrombocytopenia , and mucositis appeared to be synergistically increased in patients receiving both adriamycin and streptozotocin . Patients with abnormal pretreatment renalfunction were able to tolerate the combination therapy without undue incidence or severity of renal toxicity . Patients who developed transient streptozotocin‐related renal dysfunction were able to toleratefurther doses of streptozotocin alter their renal parameters normalized . Adriamycin in combination with streptozotocin did not offer any therapeutic advantage over adriamycin alone Various drug combinations including Adriamycin have been tested in soft tissue sarcomas , but optimal treatment remains unclear . We have evaluated Adriamycin with and without dimethyl‐triazeno‐imid‐azole‐carboxamide ( DTIC ) in the treatment of Stage III or IV and recurrent sarcomas of the uterus . Two hundred and forty cases of these rare tumors were evaluable . Of 146 evaluable patients with measurable disease , 13/80 ( 16.3 % ) of  Adriamycin‐treated patients and 16/66 ( 24.2 % ) of patients receiving the combination showed an objective response ( P > 0.05 ) . Lung metastases responded more frequently 
    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 activity and toxicity of single-agent st and ard-dose doxorubicin were compared with that of two schedules of high-dose epirubicin . A total of 334 chemonaive patients with histologically confirmed advanced soft-tissue sarcomas received ( A ) doxorubicin 75 mg m(-2 ) on day 1 ( 112 patients ) , ( B ) epirubicin 150 mg m(-2 ) on day 1 ( 111 patients ) or ( C ) epirubicin 50 mg m(-2 ) day(-1 ) on days 1 , 2 and 3 ( 111 patients ) ; all given as bolus injection at 3-week intervals . A median of four treatment cycles was given . Median age was 52 years ( 19 - 70 years ) and performance score 1 ( 0 - 2 ) . Of 314 evaluable patients , 45 ( 14 % ) had an objective tumour response  ( eight complete response , 35 partial response ) . There were no differences among the three groups . Median time to progression for groups A , B and C was 16 , 14 and 12 weeks , and median survival 45 , 47 and 45 weeks respectively . Neither progression-free ( P = 0.93 ) nor overall survival ( P = 0.89 ) differed among the three groups . After the first cycle of therapy , two patients died of infection and one owing to cardiovascular disease , all on epirubicin . Both dose schedules of epirubicin were more myelotoxic than doxorubicin .  Cardiotoxicity ( > or = grade 3 ) occurred in 1 % , 0 % and 2 % respectively . Regardless of the schedule , high-dose epirubicin is not a preferred alternative to st and ard-dose doxorubicin in the treatment of patients with advanced soft-tissue sarcomas Eighty-three patients with advanced soft tissue sarcoma who had received no prior chemotherapy entered a r and omised phase II study comparing carminomycin ( CMM ) 20 mg/m2 with adriamycin ( ADM ) 75 mg/m2 , both administered i.v . bolus every 3 weeks . Six patients were ineligible and response could not be evaluated in 6 additional patients . Thirty-eight evaluable patients received ADM and 33 received CMM . There was one complete response to ADM and 10 partial responses , an overall response rate of 29 % . CMM showed significantly ( P = 0.01 ) lower antitumour activity -- one partial response ( 3 % ) . Stabilisation of disease was similar in both arms ( 47 and 45 % ) , but fewer patients progressed on ADM ( 24 compared to 52 % ) . Duration s of response dating from the start of chemotherapy were 5 months for complete remission on ADM , a median of 7 months ( range 4 - 17 ) for partial response on ADM and 14 months for the one partial remission on CMM . Although the median time to progression for all patients receiving CMM ( 2 months ) was significantly ( P = 0.001 ) shorter than for those receiving ADM ( 5 months ) , patients on ADM had only a marginally significant longer duration of survival ( P = 0.06 ) than the patients receiving CMM . A leucocyte nadir less than 2.0 X 10(9)/l occurred in 38 % of patients receiving ADM and 43 % receiving CMM .  Anaemia and thrombocytopoenia were uncommon . Other toxicities such as nausea , vomiting , anorexia and alopecia were more severe in the ADM group . There was one infective death secondary to leucopoenia in the ADM arm , and one patient who had received 109 mg/m2 CMM + 255 mg/m2 ADM developed progressively fatal cardiomyopathy PURPOSE The aim of this trial was to compare the activity and toxicity of single-agent doxorubicin with that of two multidrug regimens in the treatment of patients with adult advanced soft tissue sarcomas . PATIENTS AND METHODS This was a prospect i ve r and omized phase III trial performed by 35 cancer centers within the Soft Tissue and Bone Sarcoma Group of the European Organization for Research and Treatment of Cancer ( EORTC ) . Six hundred sixty-three eligible patients were r and omly allocated to receive either doxorubicin 75 mg/m2 ( arm A ) , cyclophosphamide , vincristine , doxorubicin , and dacarbazine ( CYVADIC ) ( arm B ) , or ifosfamide 5 g/m2 plus doxorubicin 50 mg/m2 ( arm C ) . RESULTS The overall response rate was 24 % ( 95 % confidence interval , 20.7 % to 27.3 % ) among eligible patients and 26 % among assessable patients . No statistically significant difference was detected among the three study arms in terms of response rate ( arm A , 23.3 % ; arm B , 28.4 % ; and arm C , 28.1 % ) , remission duration ( median , 46 weeks on arm A , 48 weeks on arm B , and 44 weeks on arm C ) , or overall survival ( median , 52 weeks on arm A , 51 weeks on arm B , and 55 weeks on arm C ) . The degree of myelosuppression was significantly greater for the combination of ifosfamide and doxorubicin than for the other two regimens . Cardiotoxicity was also more frequent in this arm , but other toxicities were similar . CONCLUSION In advanced soft tissue sarcomas of adults , single-agent doxorubicin is still the st and ard chemotherapy against which more intensive or new drug treatments should be compared . Combination chemotherapy can not be recommended outside a controlled clinical trial with the exclusion of some subsets of sarcoma patients for whom significant tumor volume reduction may be an important end point of a chemotherapy regimen Ifosfamide ( IFOS ) 5 g/m2 and its parent analog Cyclophosphamide ( CYCLO ) 1.5 g/m2 were studied in a r and omized phase II study , accruing 171 patients with advanced soft tissue sarcoma . Both drugs were administered as 24 hr infusions , every 3 weeks , with comcomitant Mesna 400 mg/m2 i.v . bolus 4 hourly X 9 doses . Twenty-four patients were ineligible and 12 were not evaluable . The groups were well matched for age , previous chemotherapy ( 42 % of the total ) or radiotherapy , the presence of distant metastases and performance status , but there were more females ( 59 % vs. 45 % ) in the IFOS arm . Among the 68 evaluable patients receiving IFOS , there were 2 CR , 10 PR ( overall response 18 % ) , 27 SD and 29 PD . For CYCLO , the corresponding results in 67 patients were 1 CR , 4 PR ( overall response 8 % ) , 23 SD and 39 PD . Using the chi-square test the P values for response rate and linear trend were 0.13 and 0.04 respectively . Response rates were higher for females ( 20 % vs. 5 % , P = 0.01 ) and patients who had not received previous chemotherapy ( 19 % vs. 4 % , P = 0.01 ) . Fourteen of the 17 responses came from a group of 43 females , who had not received previous chemotherapy , for whom the overall response rate was 37.5 % . Remissions were noted in only 4 histological subtypes ( central ly review ed material ) , i.e. , 5 of 17 synovial sarcomas , 7 of 13 mixed mesodermal sarcomas and 2 of 7 fibrosarcomas . One of the 31 leiomyosarcomas responded to Cyclophosphamide .  Duration s of response did not differ significantly between the 2 arms -- median 26 , range 10 - 81 + weeks . Leucopenia was significantly more severe on CYCLO , particularly in patients who had received previous chemotherapy ( P = 0.007 ) . Serious infections occurred in approx . 7 % of patients with no difference between the two drugs , although there was one toxic death on CYCLO .  Nausea and vomiting were significantly worse on  IFOS  and alopecia , related in extent to dose , was seen in both arms . Other side-effects , such as hematuria or rises in serum creatinine and encephalopathy , were infrequent and mild . A higher response rate with less myelosuppression suggests that IFOS may have advantages over CYCLO in combination therapy Recurrent or metastatic uterine sarcoma represents an ominous and aggressive form of malignant disease . In an attempt to define a beneficial treatment program , we compared treatment with doxorubicin ( A ) 60 mg/m2 versus a combination of doxorubicin 60 mg/m2 and cyclophosphamide 500 mg/m ( CA ) , each regimen given every 3 weeks . Of 132 patients entered on study , 104 were eligible ; 50 received A and 54 CA . Pretreatment characteristics were similar , and no patient had received prior chemotherapy . The proportion of complete responses ( CR ) + partial responses ( PR ) for measurable disease patients was 5 of 26 ( 19 % ) for both A and CA . Multivariate analysis done on progression‐free interval ( PFI ) and survival ( S ) showed CA to be of no benefit over A ( PFI , P = 0.22 ; S , P = 0.55 ) . For both A and CA patients , measurable disease ( PFI , P = 0.002 ; S , P = 0.02 , respectively ) , performance status ( PFI , P = 0.004 ; S , P = 0.0002 ; respectively ) , and sites of residual disease ( PFI , P = 0.008 ; S , P = 0.003 , respectively ) were detected as prognostic variables . Conversely , histologic type , age , and recurrence status ( primary versus recurrent at entry ) were not prognostic indicators . These data indicate no significant benefit of CA versus A alone in patients with uterine sarcoma Forty-four of 50 adult patients with advanced soft-tissue sarcoma who had received previous chemotherapy  were evaluable for response after treatment with DTIC . The therapeutic schedule consisted of DTIC 1.2 g/m2 infused over 20 minutes , and repeated every 3 weeks . There were 1 complete and 7 partial remissions ( objective activity 18 % , 95 % C.I. 7%-29 % ) , with a median duration of 8 weeks ( range 5 - 19 ) , with the complete remission lasting 1 yr . Hematologic toxicity was dose-limiting ; W.H.O. greater than or equal to 3 values were observed for WBC in 36 % , and for platelets in 26 % of patients . The non-hematologic toxicity included nausea and vomiting ( 90 % ) , a flu-like syndrome ( 49 % ) , diarrhea ( 35 % ) , pain in the infused vein ( 28 % ) and hypotensive episodes ( 4 % ) . Intermittent high-dose DTIC is active in advanced soft-tissue sarcoma and should be considered for inclusion in combination regimens In a prospect ively r and omized study , 17 evaluable patients treated with adriamycin alone , 60 mg/m2 intravenously every 3 wk , were compared with 14 patients treated with adriamycin in the same dose and schedule plus streptozotocin , 500 mg/m2/day intravenously for 5 days every 3 wk . All patients had advanced sarcomas , but none had previously received either adriamycin or streptozotocin .  Objective responses were seen in 9 patients on the single drug arm ( 4 with more than 50 % tumor shrinkage and 5 with stabilization of disease ) , and in 8 patients given the combination drug arm ( 2 with more than 50 % tumor shrinkage and 6 with stabilization oldisease ) . Duration of response and survivalfrom treatmentfor both treatment groups were similar . Transient hepatic dysfunction , renal function abnormalities , and nausea with vomiting were additive in the combination drug arm , the last two limiting therapy most . Leukopenia , thrombocytopenia , and mucositis appeared to be synergistically increased in patients receiving both adriamycin and streptozotocin . Patients with abnormal pretreatment renalfunction were able to tolerate the combination therapy without undue incidence or severity of renal toxicity . Patients who developed transient streptozotocin‐related renal dysfunction were able to toleratefurther doses of streptozotocin alter their renal parameters normalized . Adriamycin in combination with streptozotocin did not offer any therapeutic advantage over adriamycin alone Various drug combinations including Adriamycin have been tested in soft tissue sarcomas , but optimal treatment remains unclear . We have evaluated Adriamycin with and without dimethyl‐triazeno‐imid‐azole‐carboxamide ( DTIC ) in the treatment of Stage III or IV and recurrent sarcomas of the uterus . Two hundred and forty cases of these rare tumors were evaluable . Of 146 evaluable patients with measurable disease , 13/80 ( 16.3 % ) of  Adriamycin‐treated patients and 16/66 ( 24.2 % ) of patients receiving the combination showed an objective response ( P > 0.05 ) . Lung metastases responded more frequently 
    Output:
    