***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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    Input: Future progress in improving cancer therapy can be expedited by better prioritization of new treatments for phase III evaluation . Historically , phase II trials have been key components in the prioritization process . There has been a long-st and ing interest in using phase II trials with r and omization against a st and ard-treatment control arm or an additional experimental arm to provide greater assurance than afforded by comparison to historic controls that the new agent or regimen is promising and warrants further evaluation . Relevant trial design s that have been developed and utilized include phase II selection design s , r and omized phase II design s that include a reference st and ard-treatment control arm , and phase II/III design s. We present our own explorations into the possibilities of developing " phase II screening trials , " in which preliminary and nondefinitive r and omized comparisons of experimental regimens to st and ard treatments are made ( preferably using an intermediate end point ) by carefully adjusting the false-positive error rates ( alpha or type I error ) and false-negative error rates ( beta or type II error ) , so that the targeted treatment benefit may be appropriate while the sample size remains restricted . If the ability to conduct a definitive phase III trial can be protected , and if investigators feel that by judicious choice of false-positive probability and false-negative probability and magnitude of targeted treatment effect they can appropriately balance the conflicting dem and s of screening out useless regimens versus reliably detecting useful ones , the phase II screening trial design may be appropriate to apply 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 Temozolomide , an oral imidazotetrazine derivative , was given to 31 patients with advanced soft tissue sarcoma . The dose of 750 mg/m2 was divided over 5 consecutive days , and escalated to 1000 mg/m2 over 5 days at cycle 2 if myelosuppression no worse than common toxicity criteria grade 2 was noted in the first 28-day cycle . A total of 99 treatment cycles were given to 31 patients . The drug was well tolerated , with nausea and vomiting as the most common side-effects . Only one partial tumour response was documented , giving a response rate of 3.33 % , 95 % confidence interval , ( CI ) 0.1 - 17.2 % . The median time to progression was 8 weeks and the median survival was 27 weeks . These results indicate that temozolomide in this schedule is not active as second-line treatment in advanced soft tissue sarcoma INTRODUCTION Vascular endothelial growth factor ( VEGF ) is a key regulator in angiogenesis . Pre clinical and clinical data support the role of VEGF and angiogenesis in renal cell carcinoma ( RCC ) , melanoma ( M ) , and soft tissue sarcoma ( STS ) . The tyrosine kinase inhibitor SU5416 is a potent inhibitor of the VEGF receptors 1 and 2 . EXPERIMENTAL DESIGN We investigated 145 mg/m(2 ) SU5416 twice weekly in patients with advanced or metastatic RCC , M , and STS . The primary objectives were efficacy and safety . Disease assessment s were performed after 4 and 8 weeks of treatment and every 2 months thereafter . Documented stable disease ( SD ) lasting for > or =3 months was considered an antitumor response . RESULTS A group of 29 patients was entered in the RCC trial , 20 patients in the M trial , and 31 patients in the STS trial .  Response was observed in 6 ( 1 minor response and 5 SDs ) of 24 evaluable patients ( 25 % ) in the RCC group , 6 ( 1 minor response and 5 SDs ) of 26 patients ( 23 % ) in the STS group , and none of the patients in the M group . Progression-free survival ranged from 7 to 252 days ( median 59 days ) in the RCC group , from 7 to 260 days ( median 60 days ) in the STS group , and from 14 to 139 days ( median 41 days ) in the M group . Toxicities observed were those reported previously for SU5416 . CONCLUSION SU5416 single agent is well tolerated . The antitumor response was low in patients with RCC and STS , whereas no responses were seen in patients with PURPOSE Given the importance of angiogenesis in soft tissue sarcoma ( STS ) , pazopanib , an oral angiogenesis inhibitor that targets vascular endothelial growth factor receptor and platelet-derived growth factor receptor , was explored in patients with advanced STS . PATIENTS AND METHODS Patients with intermediate- or high- grade advanced STS who were ineligible for chemotherapy or who had received no more than two prior cytotoxic agents for advanced disease , who had documented progression , who had adequate performance status , and who had good organ function were eligible .  Pazopanib 800 mg was given daily . The primary end point was progression-free rate at 12 weeks ( PFR(12 weeks ) ) . Secondary end points were response , safety , and overall survival . Four different strata were studied : adipocytic STS , leiomyosarcomas , synovial sarcomas , and other STS types . A Simon two-stage design was applied ( P1 = 40 % ; P0 = 20 % ; alpha = beta = .1 ) for each stratum . Results One hundred forty-two patients were enrolled . The adipocytic STS stratum was closed after the first stage , given insufficient activity ( PFR(12 weeks ) , five [ 26 % ] of19 ) . PFR(12 weeks ) was 18 ( 44 % ) of 41 patients in the leiomyosarcoma cohort , 18 ( 49 % ) of 37 in the synovial sarcomas , and 16 ( 39 % ) of 41 in the other STS types . Compared with historical controls who were treated with second-line chemotherapy , progression-free and overall survivals were prolonged in the three cohorts in which the primary end point was reached . The most frequent drug-related toxicities were hypertension , fatigue , hypopigmentation , and nausea . Other toxicities included liver enzyme elevations , myelosuppression , and proteinuria , all of which were mostly grade s 1 to 2 . The most frequent grade s 3 to 4 toxicities were hyperbilirubinemia ( 6.3 % ) , hypertension ( 7.7 % ) , and fatigue ( 7.7 % ) . CONCLUSION Pazopanib is well tolerated in patients with relapsed , advanced STS and demonstrates interesting activity that warrants additional study in patients with leiomyosarcomas , synovial sarcomas , and other STS types PURPOSE To assess the efficacy of the marine-derived alkaloid ecteinascidin 743 ( ET-743 ) in patients with soft tissue sarcomas that progressed despite prior conventional chemotherapy and to characterize the pharmacokinetic profiles of ET-743 in this patient population . PATIENTS AND METHODS Thirty-six previously treated soft tissue sarcoma patients from three institutions received ET-743 as a 24-hour continuous intravenous ( IV ) infusion at a dose of 1,500 microg/m(2 ) every 3 weeks . Pharmacokinetic studies were also performed . Patients were restaged every two cycles for response by objective criteria . RESULTS Objective responses were observed in three patients , with one complete response and two partial responses , for an overall response rate of 8 % ( 95 % CI , 2 % to 23 % ) . Responses were durable for up to 20 months . Two minor responses ( 43 % and 47 % tumor reduction ) were observed , for an overall clinical benefit rate of 14 % . The predominant toxicities were neutropenia and self-limited transaminitis of grade 3 to 4 severity in 34 % and 26 % of patients , respectively . The estimated 1-year time to progression and overall survival rates were 9 % ( 95 % CI , 3 % to 27 % ) and 53 % ( 95 % CI , 39 % to 73 % ) , respectively . The maximum observed plasma concentration and total plasma clearance of ET-743 ( mean + /- st and ard deviation ) , 1.04 + /- 0.48 ng/mL and 35.6 + /- 16.2 L/h/m(2 ) , respectively , were consistent with previously reported values from phase I studies of the drug given as a 24-hour IV infusion . CONCLUSION ET-743 is a promising new option for the management of several histologic subtypes of sarcoma . Durable objective responses were obtained in a subset of sarcoma patients with disease progression despite prior chemotherapy . Additionally , the relatively high survival rate noted in this series of previously treated patients further justifies development of this agent PURPOSE New agents are needed for patients with metastatic uterine leiomyosarcoma who progress after treatment with doxorubicin or gemcitabine-docetaxel . Agents targeting tumor vasculature have potential for activity in leiomyosarcoma . We aim ed to assess the activity of sunitinib in patients with recurrent uterine leiomyosarcoma who had received one or two prior therapies by determining the frequency of patients who survived progression-free for at least 6 months or who achieved objective tumor response . We also aim ed to characterize the toxicity of sunitinib and to estimate time-to-progression . PATIENTS AND METHODS Eligible patients with uterine leiomyosarcoma were treated with sunitinib 50 mg by mouth daily for 4 weeks , with 2 weeks rest . Tumor response and progression-free status were assessed every 6 weeks . RESULTS Twenty-three of 25 patients enrolled were evaluable for efficacy ( two wrong histologies ) . The median number of cycles was one . Two of 23 patients achieved a partial response ( 8.7 % , 90 % two-sided , binomial confidence interval ( CI ) 1.6 - 24.9 % ) . Four patients remained progression-free at 6 months ( 17.4 % , 90 % two-sided , binomial confidence interval 6.2 - 35.5 % ) . Toxicities included : grade 3 neutropenia ( 17.4 % ) ; grade 3 thrombocytopenia ( 13 % ) ; grade 3 anemia ( 17.4 % ) ; grade s 3 - 4 lymphopenia ( 8.7 % ) ; grade s 3 - 4 fatigue ( 30 % ) ; grade 3 vomiting/diarrhea ( 21.7 % ) ; skin rash/h and -foot syndrome , grade 2 ( 13 % ) , grade 3 ( 4.3 % ) ; hypertension , grade 2 ( 39 % ) , grade 3 ( 4.3 % ) ; grade 2 decrease in cardiac ejection fraction ( 4.3 % ) , and grade 3 thrombosis ( 4.3 % ) Median progression-free survival ( PFS ) was 1.5 months . CONCLUSION Sunitinib fails to achieve sufficient objective response or sustained disease stabilization as second- or third-line treatment for uterine leiomyosarcoma BACKGROUND Doxorubicin remains one of the few drugs with consistent single agent activity in advanced Soft T 
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Nevertheless , the mOS was not significantly higher in the cases of active drugs .