***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: PURPOSE Alkylating agents have modest activity in advanced urothelial carcinoma .  Ifosfamide ( IFX ) is an agent as yet unstudied in advanced urothelial carcinoma . Despite recent advances in the treatment of this disease , there continues to be a need to identify new active agents and their toxicity spectra . Here we report results from the use of IFX in this population . PATIENTS AND METHODS Ambulatory patients with advanced urothelial carcinoma were treated with IFX 3,750 mg/m2 and mesna 2250 mg/m2 both intravenously ( IV ) daily for 2 days every 3 weeks . Significant renal and CNS toxicity required a dose change of IFX to 1,500 mg/m2 IV with mesna 750 mg/m2 IV for 5 days every 3 weeks . Doses were modified for hematologic , renal , and CNS toxicity . RESULTS Of 56 eligible patients entered onto the study , 26 received the 2-day schedule and 30 were treated on the 5-day regimen . All patients had progressive disease following prior systemic chemotherapy . There were five complete responses ( CRs ) and six partial responses ( PRs ) for an overall response rate of 20 % ( exact 95 % confidence interval [ CI ] , 10 % to 32 % ) . Renal and CNS toxicity was severe before the change in schedule , but manageable after the change . Major identified toxicities were gastrointestinal , myelosuppressive , renal , and CNS . There were four early deaths to which treatment probably contributed , but were multifactorial in etiology . CONCLUSION IFX has significant activity , but also major toxicity in a heavily cisplatin-pretreated cohort with advanced urothelial carcinoma . A modification of dose and /or schedule from that described should be considered in future trials . Combination regimens using this agent should be explored PURPOSE The purpose of this study was to characterize the activity and toxicity of irinotecan in metastatic platinum-refractory urothelial carcinoma . PATIENTS AND METHODS In a prospect i ve multi-institutional phase II clinical trial , we evaluated the activity and safety of irinotecan 350 mg/m2 ( 300 mg/m2 in patients with previous radiation therapy to the pelvis ) intravenously given every 21 days in patients with metastatic urothelial carcinoma and evidence of progression following one previous systemic chemotherapy regimen for metastatic disease that included cisplatin or carboplatin .  The primary goal of this study was to evaluate the probability of confirmed complete or partial response . RESULTS Forty eligible patients were registered between December 2003 and December 2006 . One patient had a complete response , and 1 had a partial response ( overall response rate , 5 % ; 95 % CI , 1%-17 % ) . Median progression-free survival was 2.1 months ( 95 % CI , 1.8 - 2.3 months ) . Median overall survival was 5.4 months ( 95 % CI , 3.4 - 7.1 months ) . Toxicity was similar to that reported previously for this schedule of irinotecan . CONCLUSION The response rate seen in this study is insufficient to recommend further evaluation of irinotecan in urothelial cancer that relapsed following initial platinum based chemotherapy . Investigation of novel agents for this patient population remains a priority Cisplatin‐based combination chemotherapy for patients with advanced transitional cell carcinoma ( TCC ) of the urothelium has limitations , and new therapies need to be evaluated BACKGROUND The second-line chemotherapeutic treatment for metastatic urothelial cancer ( UC ) after failure of cisplatin-based first-line therapy needs to be improved . Based on encouraging phase II data of gemcitabine and paclitaxel ( Taxol ) ( GP ) , this trial was design ed to compare a short-term ( arm A ) versus a prolonged ( arm B ) second-line combination chemotherapy of GP . PATIENTS AND METHODS Of 102 r and omized patients , 96 were eligible for analysis . Primary end point was overall survival ( OS ) . Secondary end points were progression-free survival ( PFS ) , objective response rates ( ORR ) and toxicity . RESULTS Neither OS [ arm A : 7.8 ( 95 % CI : 4.2 - 11.4 ) , arm B : 8.0 ( 95 % CI : 4.9 - 11.1 ) months ] and PFS [ arm A : 4.0 ( 95 % CI : 0 - 8.0 ) , arm B : 3.1 ( 95 % CI : 1.9 - 4.2 ) months ] nor ORR ( arm A : 37.5 % , arm B : 41.5 % ) were significantly different . On prolonged treatment , more patients experienced severe anemia ( arm A : 6.7 % versus arm B : 26.7 % grade III/IV anemia ; P = 0.011 ) . In six patients , treatment was stopped during the first cycle due to disease progression or toxicity . Two patients died due to treatment-related toxic effects . CONCLUSION Due to rapid tumor progression and toxicity at this dosage and schedule in a multicenter setting , it was not feasible to deliver a prolonged regimen . However , a high response rate of ∼40 % makes GP a promising second-line treatment option for patients with metastatic UC The purpose of the study was to assess the efficacy and toxicity of carboplatin and paclitaxel administered every 3 weeks in patients with advanced urothelial carcinoma , previously treated with cisplatin‐based therapy Background Our aim was to study the efficacy and safety of combination chemotherapy with gemcitabine plus cisplatin ( GC ) for patients with advanced urothelial carcinoma ( UC ) after failure of methotrexate , vinblastin , adriamycin , and cisplatin ( M-VAC ) chemotherapy .  Methods We studied a total of 33 patients with advanced UC . All patients were treated with M-VAC with a mean of 3.2 courses per patient and had showed disease progression or no response . Clinical and pathological features were correlated to survival rates , and the incidence and degree of toxicities were also retrospectively review ed . Results A total of 132 courses of GC with a mean of 4.0 courses per patients were undergone . Two ( 6.0 % ) complete responses and 11 ( 33.3 % ) partial responses produced an overall response rate of 39.4 % . In 55 assessable lesions , there were 2 ( 4 % ) complete responses , 13 ( 23 % ) partial responses , 31 ( 55 % ) with stable disease , and 10 ( 18 % ) with progressive disease . Overall , mean of survival time after GC chemotherapy was 10.5 months ( range , 3.0–22.9 months ) . In univariate analysis , the patients with higher serum hemoglobin or single metastasis or no liver metastasis tended to survive longer than those with lower hemoglobin or multiple metastases or existence of liver metastasis . Although grade 3–4 neutropenia was seen in 22 patients ( 66.7 % ) and grade 3–4 thrombocytopenia was seen in 10 patients ( 30.3 % ) , fatal side effects were not observed . Conclusions The combination chemotherapy with GC seems feasible with no severe side effects and may provide a survival benefit for patients with advanced UC after failure of M-VAC chemotherapy BACKGROUND Single-agent taxanes are commonly used as salvage systemic therapy for patients with advanced urothelial carcinoma ( UC ) . OBJECTIVE To study the impact of combination chemotherapy delivering a taxane plus other chemotherapeutic agents compared with single-agent taxane as salvage therapy . DESIGN , SETTING , AND PARTICIPANTS Individual patient-level data from phase 2 trials of salvage systemic therapy were used . INTERVENTIONS Trials evaluating either single agents ( paclitaxel or docetaxel ) or combination chemotherapy ( taxane plus one other chemotherapeutic agent or more ) following prior platinum-based therapy were used . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Information regarding the known major baseline prognostic factors was required : time from prior chemotherapy , hemoglobin , performance status , albumin , and liver metastasis status . Cox proportional hazards regression was used to evaluate the association of prognostic factors and combination versus single-agent chemotherapy with overall survival ( OS ) . RESULTS AND LIMITATIONS Data were available from eight trials including 370 patients ; two trials ( n=109 ) evaluated single-agent chemotherapy with docetaxel ( n=72 ) and cremophor-free paclitaxel ( n=37 ) , and six trials ( n=261 ) evaluated combination chemotherapy with gemcitabine-paclitaxel ( two trials , with n=99 and n=24 ) , paclitaxel-cyclophosphamide ( n=32 ) , paclitaxel-ifosfamide-nedaplatin ( n=45 ) , docetaxel-ifosfamide-cisplatin ( n=26 ) , and paclitaxel-epirubicin ( n=35 ) . On multivariable analysis after adjustment for baseline prognostic factors , combination chemotherapy was independently and significantly associated with improved OS ( hazard ratio : 0.60 ; 95 % confidence interval , 0.45 - 0.82 ; p=0.001 ) . The retrospective design of this analysis and the trial-eligible population were inherent limitations . CONCLUSIONS Patients enrolled in trials of combination chemotherapy  exhibited improved OS compared with patients enrolled in trials of single-agent chemotherapy as salvage therapy for advanced UC . Prospect i ve r and omized trials are required to vali date a potential role for rational and tolerable combination chemotherapeutic regimens for the salvage therapy of advanced UC . PATIENT SUMMARY This retrospective study suggests that a combination of chemotherapy agents may extend survival compared with single-agent chemotherapy in selected patients with metastatic urothelial cancer progressing after prior chemotherapy OBJECTIVE The aim of this study was to evaluate the efficacy and toxicities of the gemcitabine and paclitaxel combination regimen as second-line chemotherapy for patients with advanced or metastatic urothelial carcinoma ( UC ) who have previously been treated with platinum-based chemotherapy for the metastatic disease . METHODS Thirty-three patients with advanced or metastatic UC who had received platinum-based chemotherapy  were treated with an outpatient gemcitabine and paclitaxel combination regimen . A dose of 180 mg/m(2 ) paclitaxel was administered by intravenous ( IV ) infusion on Day 1 , and 1000 mg/m(2 ) gemcitabine was administered by IV on Days 1 , 8 and 15.The course was repeated every 28 days . Patients were evaluated after every 2 cycles of therapy using computed tomography . RESULTS Of the 33 patients enrolled in this study , 30 could be evaluated to determine treatment efficacy ; 10 had an objective response [ overall response rate : 33.3 % , 95 % confidence interval ( CI ) , 19.2 - 51.2 % ] . The median overall survival was 11.3 months ( 95 % CI , 7.2 - 13.6 months ) . The chemotherapy sensitivity differed with disease site . The response rates of lung and bone metastases were 27 % and 14 % , and the progressive disease ( PD ) rates of lung and bone metastases were 13 % and 14 % , respectively . On the other h and , the response rate of liver metastasis was 14 % , and its PD rate was 57 % . None of the patients ( n = 3 ) with adrenal metastasis responded to this regimen . Toxicities were mild , and no life-threatening complications occurred . CONCLUSIONS Gemcitabine and paclitaxel combination therapy is a tolerable and active regimen for patients with advanced UC after failure of platinum-based chemotherapy A multicentre phase II trial to determine the efficacy of vinflunine as second-line therapy in patients with advanced transitional cell carcinoma ( TCC ) of the bladder ; secondary objectives were to assess duration of response , progression-free survival ( PFS ) and overall survival ( OS ) , and to evaluate the toxicity associated with this treatment . Patients had tumours that failed or progressed after first-line platinum-containing regimens for advanced or metastatic disease , or had progressive disease after platinum-containing chemotherapy given with adjuvant or neoadjuvant intent .  Response and adverse events were assessed according to WHO criteria and NCI-CTC ( version 2 ) , respectively . Out of 51 patients treated with 320 mg m−2 of vinflunine  , nine patients responded to the therapy yielding an overall response rate of 18 % ( 95 % CI : 8.4–30.9 % ) , and 67 % ( 95%CI : 52.1–79.3 % ) achieved disease control ( PR+SD ) . Of note , responses were seen in patients with relatively poor prognostic factors such as a short ( < 12 months ) interval from prior platinum therapy ( 19 % , including an 11 % response rate in those progressing <3 months after platinum treatment ) , prior treatment for metastatic disease ( 24 % ) , prior treatment with vinca alkaloids ( 14 % ) and visceral involvement (  
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No statistically significant differences in grade 3 - 4 toxicity were seen between the two groups .
Despite significant improvements in ORR and PFS , doublet regimens did not extend OS compared with single agents for the second-line chemotherapy of UC .