human
***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: OBJECTIVES To study the ablative activity of intravesical gemcitabine against superficial transitional cell carcinoma of the bladder at different doses and concentrations . METHODS A total of 27 patients were treated with intravesical gemcitabine after transurethral resection during which one to three papillary marker lesions were left unresected . Starting 14 days after transurethral resection , six instillations of gemcitabine were given at weekly intervals . Gemcitabine , diluted in 50 mL of saline solution and maintained for 2 hours , was given at the dose of 500 mg , 1000 mg , and 2000 mg in groups of 9 patients each . A complete response ( CR ) was defined as negative cytology , cystoscopy , and biopsy findings . Patients achieving a CR received monthly maintenance for up to 1 year and underwent cytology and cystoscopy at 3-month intervals . RESULTS Of the 27 patients , 1 was lost to follow-up , and of the remaining 26 patients , 6 ( 23 % ) achieved a CR . A CR was achieved in 1 patient ( 12.5 % ) , 2 patients ( 22.2 % ) , and 3 patients ( 33.3 % ) at a dose of 500 , 1000 , and 2000 mg , respectively . A partial response was obtained in 2 additional patients ( 22 % ) at a dose of 500 and 1000 mg . Bladder Tis was diagnosed in 2 patients with a CR at 3 and 8 months after treatment . The remaining 4 patients were disease free at a follow-up of up to 22 months . Systemic and local tolerability was excellent , and no treatment interruption was required . CONCLUSIONS Our experience has shown the good tolerability and potential efficacy of intravesical gemcitabine against recurrent transitional cell carcinoma of the bladder . Gemcitabine might be proposed , if our results are confirmed by larger studies , as a second-line therapy in patients who can not tolerate more aggressive intravesical therapy BACKGROUND Recurrence prophylaxis with intravesical gemcitabine ( GEM ) was effective and safe in patients with non-muscle-invasive bladder cancer ( NMIBC ) ; efficacy as single-shot instillation remains to be proved . OBJECTIVE To compare the efficacy of a single GEM instillation versus placebo ( PBO ) immediately after transurethral resection ( TUR ) of tumour in patients with histologically confirmed NMIBC ( pTa/pT1,G1 - 3 ) . DESIGN , SETTING , AND PARTICIPANTS This was a double-blind , r and omised , PBO-controlled study in patients with clinical evidence of primary or recurrent NMIBC ( Ta/T1,G1 - 3 ) . Of 355 patients r and omised at 24 urologic centres , 328 underwent TUR and received instillation ( 92.4 % ; GEM/PBO : 166/162 ) . In case of nonmalignancy , carcinoma in situ ( CIS ) , > or = pT2 disease , or intraoperative complications , patients were discontinued . INTERVENTION We used a single , postoperative 30 - 40-min instillation of GEM ( 2000 mg/100 ml of saline ) or PBO ( 100 ml of saline ) followed by continuous bladder irrigation for > or = 20 h. A second TUR ( no instillation ) and adjuvant bacillus Calmette-Guérin ( BCG ) instillations were allowed . MEASUREMENTS Primary outcome was recurrence-free survival ( RFS ) . Secondary outcomes included type of recurrence and adverse events . To detect a difference in RFS , 191 recurrences were required ( 80 % power , log-rank-test , alpha = 0.050 ) . RESULTS AND LIMITATIONS Two hundred forty-eight patients ( 69.9 % , GEM , PBO : 124 , 124 ) had histologically confirmed pTa/pT1 G1 - 3 Gx tumour and were eligible for efficacy ( GEM : 76.6 % male ; median age : 65 yr ; PBO : 83.1 % male ; median age : 67 yr ) . Treatment groups were balanced ( pTa : 75.0 % , 71.0 % ; G1-G2 : 85.5 % , 87.9 % ; recurrent tumour : 24.2 % , 21.0 % ; BCG : 10.5 % , 16.9 % ) . After a median follow-up of 24 mo , there were only 94 recurrences and 11 deaths . The study was terminated early based on predefined decision criteria . RFS was high in both groups ( 12-mo RFS [ 95 % confidence interval ( CI ) ] : GEM : 77.7 % [ 68.8 - 84.3 ] ; PBO : 75.3 % [ 66.3 - 82.3 ] ) . There was no significant group difference ( hazard ratio [ HR ] : 0.946 [ 0.64 - 1.39 ] , log-rank test , p=0.777 ) . CONCLUSIONS In this study of NMIBC , the immediate single instillation of GEM 2000 mg/100 ml of saline after TUR was not superior to PBO in terms of RFS . Rigid continuous irrigation and improved TUR/cystoscopy techniques may have contributed to the high RFS in both groups This prospect i ve study investigated the long-term effects of intravesical chemoimmunotherapy with gemcitabine ( GEM ) and bacillus Calmette-Guérin ( BCG ; n = 36 ) versus BCG alone  ( n = 51 ) for the treatment of superficial bladder cancer . For the chemoimmunotherapy ( GEM + BCG ) group , GEM ( 1000 mg ) was instilled immediately after transurethral resection of bladder tumour ( TURBT ) and again ( 2000 mg ) 1 week later . From 2 to 7 weeks after TURBT , BCG was instilled into the bladder of all patients once weekly . The recurrence-free period of the GEM + BCG group ( 24.13 months ) was significantly longer than that of the BCG monotherapy group ( 19.81 months ) . The overall recurrence rate was similar between the groups , although at 6 and 9 months post-TURBT , GEM + BCG produced a significantly lower rate of recurrence compared with BCG alone . This study suggests that intravesical chemoimmunotherapy with GEM + BCG is effective in reducing early tumour recurrence and in prolonging the recurrence-free period of superficial bladder cancer Objective : To evaluate the safety , tolerability and efficacy of adjuvant intravesical gemcitabine versus bacillus Calmette-Guérin ( BCG ) in the treatment of high-risk superficial bladder cancer . Method : 64 patients with high-risk superficial bladder cancer ( pT1 and /or G3 and /or CIS ) were assigned to interventions ( gemcitabine or BCG ) in a r and omised controlled trial . All the patients were evaluated for recurrence and progression rates ( primary endpoint ) and safety and tolerability ( secondary endpoint ) . Results : The two groups were comparable in terms of baseline characteristics . Tolerability was better for gemcitabine , whereas the BCG group experienced the need for delayed treatment or withdrawal in 12.5 % of cases . At a mean follow-up of 44 months , the recurrence rate in patients treated with BCG was 28.1 % ; the recurrence rate in patients who received gemcitabine was 53.1 % ( p = 0.037 ) . Time to recurrence was shorter in patients treated with BCG ( 25.6 vs. 39.4 months , p = 0.042 ) . No patients developed disease progression . Conclusions : Gemcitabine is significantly inferior to BCG , but given its favourable toxicity profile , it may be useful for patients intolerant to or otherwise unable to receive BCG OBJECTIVES To evaluate the response rate for intravesical gemcitabine given in three different schedules to patients with recurrent multiple carcinoma of the urinary bladder Stage Ta , grade 1 - 2 , in whom all but one marker lesion was removed . Furthermore , we sought to define the safety profile . METHODS This was a multicenter , open-label , r and omized , Phase II study in which gemcitabine 2000 mg in 100 mL of unbuffered saline was instilled as a single dose ( n = 11 ) , two doses per week for 3 weeks ( n = 11 ) , or once weekly for 6 weeks ( n = 10 ) . Efficacy was evaluated using cystoscopy after 9 weeks . Toxicity was evaluated by assessing the liver , kidney , bone marrow , and coagulation function at defined intervals and by question naire . RESULTS A total of 32 patients were included , 2 of whom were subsequently excluded because of protocol violations . The overall complete remission rate was 31 % . The respective subgroup response rate was 10 % in the single-dose group , 44 % in the once-weekly group , and 40 % in the twice-weekly group . The most common side effect was nausea . One patient withdrew because of nausea and fever , and an additional 2 patients had reversible hematologic toxicity ( mild thrombocytopenia causing delayed instillation and mild anemia ) . The side effects were generally in the multiple-dose groups , with an overrepresentation in women . Ten patients were unable to retain the drug intravesically for the full hour . CONCLUSIONS The results of our study have shown that gemcitabine has a tumor ablative effect when given intravesically for bladder cancer . A single dose seemed ineffective , and the multiple dosing regimens seemed effective . The side effects were generally mild OBJECTIVES The treatment of choice for superficial bladder TCC is endoscopic resection , followed or not by intravesical immuno/chemotherapy . Some patients are not responders to common intravesical therapy and are more exposed to disease progression . In this case the suitable treatment is radical cystectomy . Because gemcitabine is effective against advanced bladder cancer , we have initiated a study to evaluate the efficacy of its intravesical use to prevent relapse and disease progression , and tolerance and safety of this drug in patients with multi-treated bladders . In this preliminary study , we cite only data on tolerance . MATERIAL S AND METHODS 64 patients were selected , and 61 were evaluable ( age range 39 - 84 years ) , with multiple-recurrent bladder TCC . All patients were previously treated with intravesical chemotherapy and /or immunotherapy .  The protocol provided for intravesical instillation of gemcitabine ( 2000 mg ) once per week for 8 weeks . We collected data regarding problems noted by the patients ( both local and systemic ) . RESULTS 53 patients out of 61 ( 86.9 % ) completed the cycle . Side effects appeared in 14 patients , 8 of these had to suspend the treatment . Severe side effects were systemic in 4 patients ( 1 systemic edema , 1 malaise and dysgeusia , 1 hyperthermia and severe strangury , 1 elevated transaminases and asthenia ) , and local in 4 patients ( 1 severe urinary urgency , 1 hematuria , 1 urinary incontinence , and 1 case of pelvic pain ) . In 6 patients we observed pelvic pain , hematuria , strangury and UTI of medium magnitude that did not require treatment interruption . CONCLUSIONS We believe that the severe side effects requiring treatment interruption are attributable primarily to increased sensitivity in patients with multi-treated bladders . In our experience , the side effects responsible for suspension occurred at the start of treatment in 7 cases out of 8 . Our study demonstrates the safety of intravesical gemcitabine in patients with recurrent and multi-treated superficial TCC of the bladder The efficacy of intravesical gemcitabine was evaluated compared with repeated administration of bacille Calmette‐Guérin ( BCG ) after BCG failure in high‐risk , non‐muscle‐invasive bladder cancer ( BC ) OBJECTIVE Phase I studies have so far demonstrated that intravesical Gemcitabine up to a 40 mg/ml concentration is well tolerated and has a substantial ablative activity on high-risk BCG refractory SBC . New treatment options are needed for intermediate-risk SBC recurring after conventional intravesical treatments . The purpose of the present study was to investigate the ablative efficacy of intravesical Gemcitabine on intermediate-risk SBC . METHODS The study was design ed as a two-stage phase II trial , with a sample size of 39 patients . The efficacy of intravesical Gemcitabine at a concentration of 40 mg/ml ( 2000 mg in 50 ml saline solution ) administered weekly for 6 weeks was assessed on a single marker tumour left in the bladder after a complete TUR of all other lesions . Patients underwent TUR or biopsy at the site of the marker lesion 2 weeks after completion of the treatment . RESULTS Complete response was observed in 22 out of 39 patients ( 56 % ) . No progression was observed among the 17 non-responders . Neither systemic nor local side effects generally exceeded grade I toxicity . CONCLUSION The ablative effect of Gemcitabine produced a higher number of responses than the minimum required by the protocol to indicate a significant probability of drug efficacy . It is worth testing the 
    Output:
    
agent
***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: OBJECTIVES To study the ablative activity of intravesical gemcitabine against superficial transitional cell carcinoma of the bladder at different doses and concentrations . METHODS A total of 27 patients were treated with intravesical gemcitabine after transurethral resection during which one to three papillary marker lesions were left unresected . Starting 14 days after transurethral resection , six instillations of gemcitabine were given at weekly intervals . Gemcitabine , diluted in 50 mL of saline solution and maintained for 2 hours , was given at the dose of 500 mg , 1000 mg , and 2000 mg in groups of 9 patients each . A complete response ( CR ) was defined as negative cytology , cystoscopy , and biopsy findings . Patients achieving a CR received monthly maintenance for up to 1 year and underwent cytology and cystoscopy at 3-month intervals . RESULTS Of the 27 patients , 1 was lost to follow-up , and of the remaining 26 patients , 6 ( 23 % ) achieved a CR . A CR was achieved in 1 patient ( 12.5 % ) , 2 patients ( 22.2 % ) , and 3 patients ( 33.3 % ) at a dose of 500 , 1000 , and 2000 mg , respectively . A partial response was obtained in 2 additional patients ( 22 % ) at a dose of 500 and 1000 mg . Bladder Tis was diagnosed in 2 patients with a CR at 3 and 8 months after treatment . The remaining 4 patients were disease free at a follow-up of up to 22 months . Systemic and local tolerability was excellent , and no treatment interruption was required . CONCLUSIONS Our experience has shown the good tolerability and potential efficacy of intravesical gemcitabine against recurrent transitional cell carcinoma of the bladder . Gemcitabine might be proposed , if our results are confirmed by larger studies , as a second-line therapy in patients who can not tolerate more aggressive intravesical therapy BACKGROUND Recurrence prophylaxis with intravesical gemcitabine ( GEM ) was effective and safe in patients with non-muscle-invasive bladder cancer ( NMIBC ) ; efficacy as single-shot instillation remains to be proved . OBJECTIVE To compare the efficacy of a single GEM instillation versus placebo ( PBO ) immediately after transurethral resection ( TUR ) of tumour in patients with histologically confirmed NMIBC ( pTa/pT1,G1 - 3 ) . DESIGN , SETTING , AND PARTICIPANTS This was a double-blind , r and omised , PBO-controlled study in patients with clinical evidence of primary or recurrent NMIBC ( Ta/T1,G1 - 3 ) . Of 355 patients r and omised at 24 urologic centres , 328 underwent TUR and received instillation ( 92.4 % ; GEM/PBO : 166/162 ) . In case of nonmalignancy , carcinoma in situ ( CIS ) , > or = pT2 disease , or intraoperative complications , patients were discontinued . INTERVENTION We used a single , postoperative 30 - 40-min instillation of GEM ( 2000 mg/100 ml of saline ) or PBO ( 100 ml of saline ) followed by continuous bladder irrigation for > or = 20 h. A second TUR ( no instillation ) and adjuvant bacillus Calmette-Guérin ( BCG ) instillations were allowed . MEASUREMENTS Primary outcome was recurrence-free survival ( RFS ) . Secondary outcomes included type of recurrence and adverse events . To detect a difference in RFS , 191 recurrences were required ( 80 % power , log-rank-test , alpha = 0.050 ) . RESULTS AND LIMITATIONS Two hundred forty-eight patients ( 69.9 % , GEM , PBO : 124 , 124 ) had histologically confirmed pTa/pT1 G1 - 3 Gx tumour and were eligible for efficacy ( GEM : 76.6 % male ; median age : 65 yr ; PBO : 83.1 % male ; median age : 67 yr ) . Treatment groups were balanced ( pTa : 75.0 % , 71.0 % ; G1-G2 : 85.5 % , 87.9 % ; recurrent tumour : 24.2 % , 21.0 % ; BCG : 10.5 % , 16.9 % ) . After a median follow-up of 24 mo , there were only 94 recurrences and 11 deaths . The study was terminated early based on predefined decision criteria . RFS was high in both groups ( 12-mo RFS [ 95 % confidence interval ( CI ) ] : GEM : 77.7 % [ 68.8 - 84.3 ] ; PBO : 75.3 % [ 66.3 - 82.3 ] ) . There was no significant group difference ( hazard ratio [ HR ] : 0.946 [ 0.64 - 1.39 ] , log-rank test , p=0.777 ) . CONCLUSIONS In this study of NMIBC , the immediate single instillation of GEM 2000 mg/100 ml of saline after TUR was not superior to PBO in terms of RFS . Rigid continuous irrigation and improved TUR/cystoscopy techniques may have contributed to the high RFS in both groups This prospect i ve study investigated the long-term effects of intravesical chemoimmunotherapy with gemcitabine ( GEM ) and bacillus Calmette-Guérin ( BCG ; n = 36 ) versus BCG alone  ( n = 51 ) for the treatment of superficial bladder cancer . For the chemoimmunotherapy ( GEM + BCG ) group , GEM ( 1000 mg ) was instilled immediately after transurethral resection of bladder tumour ( TURBT ) and again ( 2000 mg ) 1 week later . From 2 to 7 weeks after TURBT , BCG was instilled into the bladder of all patients once weekly . The recurrence-free period of the GEM + BCG group ( 24.13 months ) was significantly longer than that of the BCG monotherapy group ( 19.81 months ) . The overall recurrence rate was similar between the groups , although at 6 and 9 months post-TURBT , GEM + BCG produced a significantly lower rate of recurrence compared with BCG alone . This study suggests that intravesical chemoimmunotherapy with GEM + BCG is effective in reducing early tumour recurrence and in prolonging the recurrence-free period of superficial bladder cancer Objective : To evaluate the safety , tolerability and efficacy of adjuvant intravesical gemcitabine versus bacillus Calmette-Guérin ( BCG ) in the treatment of high-risk superficial bladder cancer . Method : 64 patients with high-risk superficial bladder cancer ( pT1 and /or G3 and /or CIS ) were assigned to interventions ( gemcitabine or BCG ) in a r and omised controlled trial . All the patients were evaluated for recurrence and progression rates ( primary endpoint ) and safety and tolerability ( secondary endpoint ) . Results : The two groups were comparable in terms of baseline characteristics . Tolerability was better for gemcitabine , whereas the BCG group experienced the need for delayed treatment or withdrawal in 12.5 % of cases . At a mean follow-up of 44 months , the recurrence rate in patients treated with BCG was 28.1 % ; the recurrence rate in patients who received gemcitabine was 53.1 % ( p = 0.037 ) . Time to recurrence was shorter in patients treated with BCG ( 25.6 vs. 39.4 months , p = 0.042 ) . No patients developed disease progression . Conclusions : Gemcitabine is significantly inferior to BCG , but given its favourable toxicity profile , it may be useful for patients intolerant to or otherwise unable to receive BCG OBJECTIVES To evaluate the response rate for intravesical gemcitabine given in three different schedules to patients with recurrent multiple carcinoma of the urinary bladder Stage Ta , grade 1 - 2 , in whom all but one marker lesion was removed . Furthermore , we sought to define the safety profile . METHODS This was a multicenter , open-label , r and omized , Phase II study in which gemcitabine 2000 mg in 100 mL of unbuffered saline was instilled as a single dose ( n = 11 ) , two doses per week for 3 weeks ( n = 11 ) , or once weekly for 6 weeks ( n = 10 ) . Efficacy was evaluated using cystoscopy after 9 weeks . Toxicity was evaluated by assessing the liver , kidney , bone marrow , and coagulation function at defined intervals and by question naire . RESULTS A total of 32 patients were included , 2 of whom were subsequently excluded because of protocol violations . The overall complete remission rate was 31 % . The respective subgroup response rate was 10 % in the single-dose group , 44 % in the once-weekly group , and 40 % in the twice-weekly group . The most common side effect was nausea . One patient withdrew because of nausea and fever , and an additional 2 patients had reversible hematologic toxicity ( mild thrombocytopenia causing delayed instillation and mild anemia ) . The side effects were generally in the multiple-dose groups , with an overrepresentation in women . Ten patients were unable to retain the drug intravesically for the full hour . CONCLUSIONS The results of our study have shown that gemcitabine has a tumor ablative effect when given intravesically for bladder cancer . A single dose seemed ineffective , and the multiple dosing regimens seemed effective . The side effects were generally mild OBJECTIVES The treatment of choice for superficial bladder TCC is endoscopic resection , followed or not by intravesical immuno/chemotherapy . Some patients are not responders to common intravesical therapy and are more exposed to disease progression . In this case the suitable treatment is radical cystectomy . Because gemcitabine is effective against advanced bladder cancer , we have initiated a study to evaluate the efficacy of its intravesical use to prevent relapse and disease progression , and tolerance and safety of this drug in patients with multi-treated bladders . In this preliminary study , we cite only data on tolerance . MATERIAL S AND METHODS 64 patients were selected , and 61 were evaluable ( age range 39 - 84 years ) , with multiple-recurrent bladder TCC . All patients were previously treated with intravesical chemotherapy and /or immunotherapy .  The protocol provided for intravesical instillation of gemcitabine ( 2000 mg ) once per week for 8 weeks . We collected data regarding problems noted by the patients ( both local and systemic ) . RESULTS 53 patients out of 61 ( 86.9 % ) completed the cycle . Side effects appeared in 14 patients , 8 of these had to suspend the treatment . Severe side effects were systemic in 4 patients ( 1 systemic edema , 1 malaise and dysgeusia , 1 hyperthermia and severe strangury , 1 elevated transaminases and asthenia ) , and local in 4 patients ( 1 severe urinary urgency , 1 hematuria , 1 urinary incontinence , and 1 case of pelvic pain ) . In 6 patients we observed pelvic pain , hematuria , strangury and UTI of medium magnitude that did not require treatment interruption . CONCLUSIONS We believe that the severe side effects requiring treatment interruption are attributable primarily to increased sensitivity in patients with multi-treated bladders . In our experience , the side effects responsible for suspension occurred at the start of treatment in 7 cases out of 8 . Our study demonstrates the safety of intravesical gemcitabine in patients with recurrent and multi-treated superficial TCC of the bladder The efficacy of intravesical gemcitabine was evaluated compared with repeated administration of bacille Calmette‐Guérin ( BCG ) after BCG failure in high‐risk , non‐muscle‐invasive bladder cancer ( BC ) OBJECTIVE Phase I studies have so far demonstrated that intravesical Gemcitabine up to a 40 mg/ml concentration is well tolerated and has a substantial ablative activity on high-risk BCG refractory SBC . New treatment options are needed for intermediate-risk SBC recurring after conventional intravesical treatments . The purpose of the present study was to investigate the ablative efficacy of intravesical Gemcitabine on intermediate-risk SBC . METHODS The study was design ed as a two-stage phase II trial , with a sample size of 39 patients . The efficacy of intravesical Gemcitabine at a concentration of 40 mg/ml ( 2000 mg in 50 ml saline solution ) administered weekly for 6 weeks was assessed on a single marker tumour left in the bladder after a complete TUR of all other lesions . Patients underwent TUR or biopsy at the site of the marker lesion 2 weeks after completion of the treatment . RESULTS Complete response was observed in 22 out of 39 patients ( 56 % ) . No progression was observed among the 17 non-responders . Neither systemic nor local side effects generally exceeded grade I toxicity . CONCLUSION The ablative effect of Gemcitabine produced a higher number of responses than the minimum required by the protocol to indicate a significant probability of drug efficacy . It is worth testing the 
    Output:
    