***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 Cisplatin‐based combination chemotherapy for patients with advanced transitional cell carcinoma ( TCC ) of the urothelium has limitations , and new therapies need to be evaluated PURPOSE We evaluated the role of paclitaxel in patients with advanced urothelial carcinoma and renal insufficiency or as second line therapy for metastatic disease . MATERIAL S AND METHODS Nine patients with advanced urothelial carcinoma received 175 to 250 mg./m2 . paclitaxel intravenously as a 24-hour infusion . Six patients had renal insufficiency with a median serum creatinine of 2.25 mg./dl . ( range 1.9 to 3.2 ) and 3 with normal renal function were treated after disease progression following 1 to 2 prior chemotherapy regimens . RESULTS Of 9 patients 5 ( 56 % ) achieved a partial response , including 4 of 6 with renal insufficiency . Toxicity was primarily hematological with 4 patients experiencing febrile neutropenia . There was no adverse impact on renal function . CONCLUSIONS Paclitaxel as a single agent represents an effective therapeutic alternative for patients with advanced transitional cell carcinoma of the urothelium and renal insufficiency precluding cisplatin or gallium nitrate based chemotherapy . Additionally , paclitaxel appears to be effective in patients in whom prior cisplatin based therapy failed 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 BACKGROUND Based on the favorable results of the combination 5-fluorouracil ( 5-FU ) , cisplatin and interferon-alpha as second-line treatment in advanced metastatic transitional-cell carcinoma of the urothelial tract a confirmatory study was executed in a multicenter setting . PATIENTS AND METHODS In this open label phase II study 43 patients failing adequate previous chemotherapy were treated with IFN-alpha2b 5 MU/m2 subcutaneously for 5 consecutive days starting on day 1 and 22 simultaneous with 5-FU 500 mg/m2 daily as a continuous infusion . In between the same dose of IFN-alpha2b was given 3 times weekly with CDDP 25 mg/m2 on days 1 , 8 , 15 and 22 . This cycle was repeated every six weeks . RESULTS In 40 eligible patients 5 PR were seen ( 12.5 % ; 95 % confidence interval ( 95 % CI ) : 4.1%-26.8 % ) . The major toxicity was hematological . Two toxic deaths were seen due to gastrointestinal hemorrhage . CONCLUSIONS In view of these results this combination can not be recommended as second line treatment for metastatic transitional-cell carcinoma of the urothelial tract 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 Objectives : i ) To evaluate objective response , toxicity , and quality of life ( QoL ) of gemcitabine monotherapy as second-line treatment in patients with cisplatin-refractory , metastatic transitional cell carcinoma ( TCC ) . ii ) To assess prognostic parameters for response to treatment and for improvement of QoL parameters . Patients and Methods : 30 patients were prospect ively enrolled in this open-label , nonr and omized multicenter phase II trial . Patients received up to 6 courses of gemcitabine monotherapy ( 1,250 mg/m2 on day 1 and 8 of a 21-day course ) . 28 of 30 patients were available for response evaluation . Results : Objective response ( OR ) was seen in 3/28 ( 11 % ) of patients ( 2 complete remissions , 1 partial remission ) . The mean time to progression ( TTP ) was 4.9 ± 3.5 months and mean disease-specific survival time was 8.7 ± 4.7 months . 13 of 28 patients did not progress ( OR + 10 stable diseases ) , and TTP ( 8.0 ± 2.7 months , p < 0.001 ) as well as survival time ( 10.2 ± 3.8 months , p < 0.05 ) differed significantly from those who showed progressive disease within 18 weeks of treatment . Pain values significantly improved in the group of responders from 4.3 ± 1.9 to 5.8 ± 1.3 points ( p < 0.05 ) . Response to cisplatin  pretreatment was the best prognosticator for the response to gemcitabine . Conclusions : Gemcitabine monotherapy as second-line treatment is justified in patients with metastatic TCC who are refractory to cisplatin treatment . Patients with initially OR  to cisplatin  benefit most from second-line treatment . QoL remains stable during treatment , and pain improves especially in patients with bone metastases 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 Background To evaluate the efficacy and toxicity of a combination chemotherapy consisting of gemcitabine , carboplatin , and docetaxel ( GCD ) in patients with advanced urothelial carcinoma ( UC ) as a phase II trial . Material s and methods Patients with metastatic or locally advanced unresect 
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As for grade 3 and 4 toxicities , more frequencies of leukopenia and thrombocytopenia were observed in the combined chemotherapy than in single agent group , while equivalent frequencies of anemia , nausea , vomiting , and diarrhea were found between the two groups .
Conclusion In comparison with single agent alone , combined chemotherapy as salvage treatment for advanced UC patients significantly improved ORR , DCR , and 1-year OS , but not 2-year OS .