***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 A non-r and omised , phase 2 study showed activity and tolerability of eribulin in advanced or metastatic soft-tissue sarcoma . In this phase 3 study , we aim ed to compare overall survival in patients with advanced or metastatic soft-tissue sarcoma who received eribulin with that in patients who received dacarbazine  ( an active control ) . METHODS We did this r and omised , open-label , phase 3 study across 110 study sites in 22 countries . We enrolled patients aged 18 years or older with intermediate- grade or high- grade advanced liposarcoma or leiomyosarcoma who had received at least two previous systemic regimens for advanced disease ( including an anthracycline ) . Using an interactive voice and web response system , an independent statistician r and omly assigned ( 1:1 ) patients to receive eribulin mesilate ( 1·4 mg/m(2 ) intravenously on days 1 and 8) or dacarbazine ( 850 mg/m(2 ) , 1000 mg/m(2 ) , or 1200 mg/m(2 ) [ dose dependent on centre and clinician ] intravenously on day 1 ) every 21 days until disease progression . R and omisation was stratified by disease type , geographical region , and number of previous regimens for advanced soft-tissue sarcoma and in blocks of six . Patients and investigators were not masked to treatment assignment . The primary endpoint was overall survival in the intention-to-treat population . The study is registered with Clinical Trials.gov , number NCT01327885 , and is closed to recruitment , but treatment and follow-up continue . FINDINGS Between March 10 , 2011 and May 22 , 2013 , we r and omly assigned patients to eribulin ( n=228 ) or dacarbazine ( n=224 ) . Overall survival was significantly improved in patients assigned to eribulin compared with those assigned to dacarbazine ( median 13·5 months [ 95 % CI 10·9 - 15·6 ] vs 11·5 months [ 9·6 - 13·0 ] ; hazard ratio 0·77 [ 95 % CI 0·62 - 0·95 ] ; p=0·0169 ) . Treatment-emergent adverse events occurred in 224 ( 99 % ) of 226 patients who received eribulin and 218 ( 97 % ) of 224 who received dacarbazine  . Grade 3 or higher adverse events were more common in patients who received eribulin ( 152 [ 67 % ] ) than in those who received dacarbazine ( 126 [ 56 % ] ) , as were deaths ( 10 [ 4 % ] vs 3 [ 1 % ] ) ; one death ( in the eribulin group ) was considered treatment-related by the investigators . INTERPRETATION Overall survival was improved in patients assigned to eribulin compared with those assigned to an active control , suggesting that eribulin could be a treatment option for advanced soft-tissue sarcoma . FUNDING Eisai AIM This r and omised phase III trial evaluated first-line trabectedin versus doxorubicin-based chemotherapy ( DXCT ) in patients with advanced/metastatic translocation-related sarcomas ( TRS ) . METHODS Patients were r and omly assigned ( 1:1 ) to receive trabectedin 1.5mg/m2 24-h intravenous ( i.v . ) infusion every 3 weeks ( q3wk ) ( Arm A ) , or doxorubicin 75 mg/m2 i.v . , q3wk , or doxorubicin 60 mg/m2 i.v . plus ifosfamide ( range , 6 - 9 g/m2 ) i.v . q3wk ( Arm B ) . Progression-free survival ( PFS ) by independent review was the primary efficacy end-point . RESULTS One hundred and twenty-one patients were r and omised ; 88 of them had TRS confirmed by central pathology review ( efficacy population ) . Twenty-nine PFS events were assessed by independent review ( 16 with trabectedin ; 13 with DXCT ) . PFS showed non-significant difference between arms ( stratified log rank test , p=0.9573 ; hazard ratio=0.86 , p=0.6992 ) . At the time of this analysis , 63.9 % and 58.3 % of patients were alive in trabectedin and DXCT arms , respectively . There was no statistically significant difference in survival curves . Response rate according to Response Evaluation Criteria in Solid Tumours ( RECIST ) v.1.0 was significantly higher in DXCT arm ( 27.0 % versus 5.9 % ) , but response according to Choi criteria showed fewer differences between treatment arms ( 45.9 % versus 37.3 % ) . Safety profile was as expected for both arms , with higher incidence of severe neutropenia , alopecia and mucositis in the DXCT arm . CONCLUSION Neither trabectedin nor doxorubicin-based chemotherapy showed significant superiority in the first-line treatment of patients with advanced translocation-related sarcoma A total of 144 patients with advanced sarcomas were entered into a r and omized prospect i ve protocol with four treatment arms utilizing different combinations of chemotherapeutic agents . Of these , 120 patients ( 83 % ) were judged acceptable . Treatment 1 : actinomycin-D ( Act-D ) , 0.01 mg/kg IV , days 1 - -5 ; phenylalanine mustard ( L-PAM ) , 4 mg PO , days 1 - -10 every six weeks . Treatment 2 : Act-D , 0.01 mg/kg IV , days 1 - -5 ; L-PAM , 4 mg PO , days 1 - -10 ; vincristine , 1 mg IV , days 1 , 8 , 15 , 22 , 29 , 36 , repeat every six weeks . Treatment 3 : Act-D , 0.01 mg/kg IV , days 1 - -5 ; L-PAM , 4 mg PO , DAYS 1 - -10 ; NSC-1026 , 200 mg/kg IV , days 1 - -6 . Treatment 4 : Adriamycin , 0.4 mg/kg IV , days 1 , 2 , 3 , 8 , 9 , 10 , then 2XWK starting day 15 ( max . 1,200 mg ) . There was a provision that upon progression of the disease in the first three treatment regimens , patients would be crossed over to Treatment 4 . Responses were as follows : 1 - Partial Response ( PR ) 1/25 ; No Change ( NC ) 9/25 ( 36 % ) . gF2 - NC 17/26 ( 65 % ) . 3 - NC 13/25 ( 52 % ) . 4 - Complete Response ( CR ) 1/41 ; PR 6/41 ; ( 15 % ) ; NC 27/41 ( 66 % ) . Clearly Treatment 4 was the best arm , with a 17 % response rate and an initial progression rate of 17 % . The only other response was a partial in 1 . The difference is statistically significant ( H = 17.247 , P = 0.0006 ) . If the responders to Adriamycin were analyzed without crossovers , the response rate would be 22 % ( 6/27 ) . ( H = 14.079 , P = 0.003 ) . Median times to progression were 12.5 , 8.7 weeks for 1 and 2 , and 5 weeks for 3 and 4 . There was no significant difference in the median survival times among the four treatment arms . It appears that Adriamycin as a single drug is superior to the drug combinations and would probably be even more effective used in combination with known active agents 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 In this patient series , doxorubicin and cycloleucine at a dose of 300 mg/kg both show response rates in the treatment of advanced soft tissue sarcomas of about 15 % . Lower doses of cycloleucine ( 200 mg/kg ) yielded less toxicity but were less effective against the sarcomas ( 6 % response rate , three of 51 patients ) . There were no complete responses with cycloleucine and there were three with doxorubicin .  Survival times for patients receiving doxorubicin were significantly longer than those of patients receiving  cycloleucine  at doses of 300 mg/kg ( P less than 0.001 ) or 200 mg/kg ( P = 0.02 ) . The estimated survival times were 29 weeks for doxorubicin and 21 ( 300 mg/kg ) and 18 ( 200 mg/kg ) weeks for cycloleucine .  Toxic effects due to cycloleucine were excessive , with severe thrombocytopenia and central nervous system depression being the most prominent 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 ( CYV 
    Output:
    
The median OS was significantly prolonged in RCTs published after 2012 when pazopanib was approved for treating ASTS .
Conclusions The trial-level correlation between PFS and OS was only modest ; it tended to be better in RCTs published after 2012 .
While the effective lines of chemotherapy and the introduction of new drugs prolonged OS but not PFS , PFS is a better surrogate than other intermediate endpoints in the first-line ASTS trials even in the post-pazopanib era .
Although this does not negate the need for more reliable surrogate endpoints for OS