***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 
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    ***EXAMPLES*** 
    Input: PURPOSE This nonr and omized multicenter phase II study was performed to evaluate the activity and safety of Ecteinascidin ( ET-743 ) administered at a dose of 1.5 mg/m(2 ) as a 24-hour continuous infusion every 3 weeks in patients with pretreated advanced soft tissue sarcoma . PATIENTS AND METHODS Patients with documented progressive advanced soft tissue sarcoma received ET-743 as second- or third-line chemotherapy .  Antitumor activity was evaluated every 6 weeks until progression , excessive toxicity , or patient refusal . RESULTS One hundred four patients from eight European institutions were included in the study ( March 1999 to November 2000 ) . A total of 410 cycles were administered in 99 assessable patients . Toxicity mainly involved reversible grade 3 to 4 asymptomatic elevation of transaminases in 40 % of patients , and grade 3 to 4 neutropenia was observed in 52 % of patients . There were eight partial responses ( PR ; objective regression rate , 8 % ) , 45 no change ( NC ; > 6 months in 26 % of patients ) , and 39 progressive disease . A progression arrest rate ( PR + NC ) of 56 % was observed in leiomyosarcoma and 61 % in synovialosarcoma . The median duration of the time to progression was 105 days , and the 6-month progression-free survival was 29 % . The median duration of survival was 9.2 months . CONCLUSION ET-743 seems to be a promising active agent in advanced soft tissue sarcoma , with no cumulative toxicities . The 6-months progression-free survival observed in advanced soft tissue sarcoma compares favorably with those obtained with other active drugs tested in second-line chemotherapy in previous European Organisation for the Research and Treatment of Cancer trials . The median overall survival was unusually long in these heavily pretreated patients mainly due to the high number of patients who benefit from the drug in terms of tumor control Purpose and Methods : Bone and soft tissue sarcomas currently comprise 1 % of adult malignancies and 15 % of pediatric malignancies [ 1 ] . While doxorubicin and ifosfamide are active agents , no significant impact on survival has been observed . More active regimes are required in sarcoma . This trial studied cisplatin and a 5 day continuous infusion of vinblastine for patients who had had disease progression of advanced soft tissue sarcoma after a doxorubicin based regimen .  Results : Between July 1983 and October 1986 , 20 patients entered the study . There were no treatment related deaths . Seven patients required dose adjustment for neutropenia . No responses were observed In this phase II study the effect of high-dose ifosfamide ( HDI ) given as a 3-day continuous infusion at a dose of 12 g/m2 repeated every 4 weeks with adequate mesna protection and hydration was evaluated in patients with advanced soft tissue sarcomas . A total of 124 patients entered the trial of which 10 were ineligible .  HDI was given both as first-line and second-line chemotherapy .  Median age was 46 years ( 19 - 66 years ) . Median World Health Organization ( WHO ) performance status was 1 ( 0 - 1 ) . Fifty two per cent of the patients were males . The predominant histology was leiomyosarcoma ( 33 % ) . A maximum of six cycles was given . At the time of analysis 55 patients have died . The partial response ( PR ) rate was 16 % . The median time to progression was 15 weeks . 8 of the 18 responding patients ( 44 % ) had synovial sarcomas , whereas only 5 % of the patients having leiomyosarcomas responded . The grade 3 + 4 haematological toxicity encountered was neutrophils in 78 % and platelets in 12 % . The major grade 3 + 4 non-haematological toxicities encountered were febrile neutropenia in 39 % , infection in 20 % , and acute renal failure in 4 % . In conclusion , it is possible to administer HDI on a multicentre basis , but the toxicity is substantial . HDI given as a continuous infusion at this dose can not be recommended as the st and ard treatment of advanced soft tissue sarcomas , even in selected patients Purpose : Based on the promising results of a Phase I study with a combination of gemcitabine and DTIC performed in advanced soft tissue sarcoma ( ASTS ) patients , and due to the limited efficacy of second or third line therapies in those patients , we design ed a Phase II study to determine the activity of this new regimen . Methods : Patients with ASTS , measurable disease , pretreated with chemotherapy , received gemcitabine 1,800 mg/m2 infused over 180 min followed by DTIC 500 mg/m2 ( one cycle ) , every 2 weeks . The pharmacokinetics ( PK ) of gemcitabine and 2′,2′-difluorodeoxyuridine ( dFdU  ) , and the accumulation of gemcitabine triphosphate ( dFdCTP ) by peripheral blood mononuclear cells were studied . The influence of the sequence of administration on those parameters was examined to exclude potential drug interactions . Results : Twenty-six patients received a total of 158 cycles ( mean four cycles , range 1–18 ) . Grade 3–4 anemia ( 23 % of patients ) , granulocytopenia ( 46 % ) or thrombocytopenia ( 12 % ) , and grade 3 increase in AST ( 18 % ) , ALT ( 21 % ) , or γ-glutamyl-transferase ( 9 % ) were noted . Response rate in 23 patients was 4 % ( 95 % CI : 0–24 % ) , and in 8 of 11 patients stable disease lasted > 6 months . Progression-free rate ( PFR ) at 3 and 6 months was , respectively , 48 and 28 % , and median overall survival 37 weeks . Pooled data from the Phase I and Phase II studies showed clinical benefit in patients with leiomyosarcomas ( LMS ) ( 57 % ) and malignant fibrous histiocytomas ( MFH ) ( 33 % ) . The sequence of administration did not influence PK of gemcitabine or dFdU. There was a trend ( P = 0.11 ) toward a lower accumulation of dFdCTP when DTIC preceded gemcitabine . Conclusions : Although the remission rate was low , PFR figures indicate that this regimen has activity in patients with ASTS . It should be compared with DTIC , or other gemcitabine-containing combinations , in patients with LMS or MFH , to determine whether this combination offers advantages in PFR or in overall activity 10529 Background : Dacarbazine ( D ) and gemcitabine ( G ) are active as single agents in the treatment of patients ( pts ) with advanced soft tissue sarcoma ( STS ) resistant to st and ard chemotherapy . The purpose of this study was to assess if the combination of D and G ( Buesa et al. Cancer . 2004;101:2261 ) improved clinical outcome compared with st and ard D. METHODS Pts with advanced STS progressing after doxorubicin and ifosfamide , PS 0 - 2 , no prior G or D , measurable disease and adequate organ function , were r and omized to receive  G 1,800 mg/m2 as a fixed dose infusion rate ( 10 mg/m2/min ) and D 500 mg/m2 every 2 weeks , or D 1,200 mg/m2 alone every 3 weeks . Pts were stratified by PS and interval since the initial diagnosis . The primary endpoint was progression-free rate ( PFR ) at 3 months , based on EORTC reference values . A one- sample binomial design was used . To detect an increase in PFR at 3 months from 40 % to 60 % with a power of 80 % and a two-sided alpha of 0.05 , 49 pts had to be accrued per arm ( an additional 10 % was permitted , to allow for pts who could not be evaluated ) . RESULTS From November 2005 to September 2008 , 113 pts from 18 centers were r and omized . 3 pts were ineligible . Baseline characteristics were well-balanced between both arms . The median number of cycles administered of D+G and D were 6 ( 2 - 13 ) and 2 ( 1 - 10 ) , respectively . PR and SD > 12 weeks rates were 9 % and 38 % ( D+G ) vs. 4 % and 19 % ( D ) respectively ( p=.01 ) . PFR at 3 months was 59 % ( D+G ) vs. 35 % ( D ) ( p=.001 ) . 29 pts were free of progression at 3 months among the first 49 pts in the D+G arm ( 26 required to be the study positive ) . Median progression-free survival was 4.4 ( D+G ) vs. 1.9 ( D ) months ( p=.002 ) . Median overall survival was 17.1 ( D+G ) vs. 9.9 ( D ) months ( p=.007 ) . Asthenia , emesis and stomatitis were the most common nonhematologic effects . Severe anemia and thrombocytopenia were more frequent with D and granulocytopenia with D+G. CONCLUSIONS The combination of D plus G is active and well-tolerated in pts with pretreated STS , yielding significant improvement in survival . No significant financial relationships to disclose Summary Background : The number of effective cytotoxic agents for the treatment of patients with metastatic adult type soft tissue sarcoma ( STS ) is limited , when patients have failed anthracyline-based chemotherapy .  The aim of this trial was to evaluate the efficacy of gemcitabine in this setting . Methods : Between August 2001 and March 2003 19 patients were eligible to enter .  Gemcitabine was administered as a 30-minutes infusion at a dosage of 1 g/m2 on day 1 , 8 and 15 every 4 weeks . All patients had progressive disease during ( n = 12 ) or shortly after an anthracycline-based regimen ( n = 3 ) . Results : Four of 19 patients did not start study treatment because of fulminant progression .  Fifteen patients with a median age 47 years ( 32–72 ) were assessable . All patients had received at least one prior treatment regimen ( range , 1–6 ) for metastatic disease containing anthracyclines ( n = 15 ) and ifosfamide ( n = 11 ) . To date , a total of 72 + cycles have been applied ( median ; 3 , 1–28 + ) . Seven patients ( 47 % ) had progressive disease after completion of two cycles at the first response assessment . One patient ( 6 % ) attained a partial remission , and 7 patients ( 47 % ) achieved disease stabilisations . One patient is still on treatment after more than 2.5 years . The calculated progression-free rate at 3 and 6 months was 46.7 % ( CI95 % , 21.4–71.9 ) and 13.3 % ( CI95 % , ( 0–30.5 ) . 95 % of the cycles have been applied without any dose modification or treatment delay . Conclusions : Considering response and progression-free rate as the primary endpoints for phase II trials in pretreated STS , gemcitabine has moderate efficacy RATIONALE Advanced synovial sarcomas ( SyS ) refractory to doxorubicin and ifosfamide are highly resistant to the currently available cytotoxic agents . Based on a report showing a specific overexpression of HER-1 in SyS , we investigated an HER-1 inhibitor , gefitinib , in refractory SyS. SUBJECTS AND METHODS To establish the efficacy and safety of gefitinib in HER-1 - positive SyS refractory to one or two lines of doxorubicin- and ifosfamide-based chemotherapy  , a phase II study was conducted from December 2002 to October 2005 by 12 centers of the European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group .  Gefitinib was given at a 500-mg/day oral dose until progression or intolerance . RESULTS Forty-eight patients were included ( 46 eligible ) . All patients had previously received chemotherapy for metastatic disease , with a median number of two lines ( range , 1 - 4 ) . The most frequent metastatic sites were the lungs ( n = 44 , 92 % ) , lymph nodes ( n = 11 , 23 % ) , and soft tissues ( n = 10 , 21 % ) . The median duration of treatment was 43 days ( range , 13 - 315 ) . Treatment was interrupted in five patients ( 10 % ) . Treatment was halted for progression in 45 ( 94 % ) patients . The best response was stable disease in 10 patients ( 21 % ) . Disease progression occurred in 32 patients ( 70 % ) , with a median time to disease progression of 6 weeks . Progression-free survival at 4 and 6 months was 21 % and 6 % , respectively . CONCLUSION The results show that gefitinib monotherapy in advanced SyS refractory to conventional chemotherapy did not demonstrate sufficient activity to warrant further investigation in this setting . This may suggest 
    Output:
    
Conclusions Across the RCTs , pazopanib over placebo , gemcitabine-dacarbazine over dacarbazine , and trabectedin 3-weekly over weekly regimen clearly demonstrated a PFS advantage in the second- and later-line treatment of advanced STS .