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: BACKGROUND The optimal dose and duration of intravesical bacillus Calmette-Guérin ( BCG ) in the treatment of non-muscle-invasive bladder cancer ( NMIBC ) are controversial . OBJECTIVE To determine if a one-third dose ( 1/3D ) is not inferior to the full dose ( FD ) , if 1 yr of maintenance is not inferior to 3 yr of maintenance , and if 1/3D and 1 yr of maintenance are associated with less toxicity . DESIGN , SETTING , AND PARTICIPANTS After transurethral resection , intermediate- and high-risk NMIBC patients were r and omized to one of four BCG groups :  1/3D-1 yr , 1/3D-3 yr , FD-1 yr , and FD-3 yr . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The trial was design ed as a noninferiority study with the null hypothesis of a 10 % decrease in the disease-free rate at 5 yr . Times to events were estimated using cumulative incidence functions and compared using the Cox proportional hazards regression model . RESULTS AND LIMITATIONS In an intention-to-treat analysis of 1355 patients with a median follow-up of 7.1 yr , there were no significant differences in toxicity between 1/3D and FD . The null hypotheses of inferiority of the disease-free interval for both 1/3D and 1 yr could not be rejected . We found that 1/3D-1 yr is suboptimal compared with FD-3 yr ( hazard ratio [ HR ] : 0.75 ; 95 % confidence interval [ CI ] , 0.59 - 0.94 ; p=0.01 ) . Intermediate-risk patients treated with FD do not benefit from an additional 2 yr of BCG . In high-risk patients , 3 yr is associated with a reduction in recurrence ( HR : 1.61 ; 95 % CI , 1.13 - 2.30 ; p=0.009 ) but only when given at FD . There were no differences in progression or survival . CONCLUSIONS There were no differences in toxicity between 1/3D and FD . Intermediate-risk patients should be treated with FD-1 yr . In high-risk patients , FD-3 yr reduces recurrences as compared with FD-1 yr but not progressions or deaths . The benefit of the two additional years of maintenance should be weighed against its added costs and inconvenience . TRIAL REGISTRATION This study was registered at Clinical Trials.gov , number NCT00002990 ; http:// clinical trials.gov/ct2/show/record/NCT00002990 BACKGROUND Intravesical instillation of bacillus Calmette-Guérin ( BCG ) is the most efficient strategy for prophylaxis of superficial bladder cancer recurrence .  Adverse effects of BCG are major obstacles , but the reduction of BCG dose could minimize these effects . The efficacy and adverse effects of half-dose ( 40 mg ) BCG , Tokyo 172 strain , were prospect ively evaluated . METHODS A total of 93 patients with superficial bladder cancer ( pTa or pT1 ) were sequentially assigned to receive either 40 or 80 mg of BCG after transurethral resection . BCG was administered weekly for 6 weeks postoperatively . Eighty patients observed longer than 12 months after BCG therapy ( 41 , 40 mg group ; 39 , 80 mg group ) were analyzed . RESULTS BCG therapy course was completed in 71 patients . Tumor recurrence was recognized in 11 of 40 patients in the 40 mg group and in 5 of 31 patients in the 80 mg group . There was no significant difference in tumor recurrence rate between the two groups ( P = 0.547 ) . BCG therapy was withdrawn in 1 patient in the 40 mg group and in 8 patients in the 80 mg-group because of BCG-related adverse effects . The morbidity of BCG-related toxicity was significantly higher in the 80 mg group . CONCLUSION Half-dose of BCG Tokyo 172 strain had a similar efficacy and its toxicity was significantly lower compared to the st and ard dose . Thus , half-dose of this strain might be suitable , at least for initial BCG therapy , for the prophylaxis of bladder cancer recurrence . Further study would be necessary to clarify the efficacy of low-dose instillation in high-risk patients PURPOSE We evaluated the efficacy of perioperative mitomycin C ( MMC ) instillation to improve subsequent  bacillus Calmette-Guérin ( BCG )  instillation efficacy in intermediate and high risk patients with non-muscle invasive bladder cancer ( NMIBC ) . MATERIAL S AND METHODS From November 2004 to May 2006 , 51 patients with intermediate or high risk NMIBC were enrolled in this prospect i ve r and omized trial . In group A , patients were treated with perioperative MMC ( 40 mg MMC in 40 mL saline was administered within 6 hours of surgery ) followed by delayed ( at least 15 days from surgery ) BCG instillations ( once a week for 6 weeks , 5 x 108 colony-forming units in 50 mL saline ) . Patients in group B were treated with delayed BCG instillations alone . The primary end points were recurrence-free interval and recurrence rate . RESULTS There were 25 and 26 patients in groups A and B , respectively . Median follow-up was 41.3 months ( range 8 to 64 ) in group A and 40.9 months ( range 6 to 68 ) in group B. Recurrence rate was 36 % ( 9 of 25 ) and 19.3 % ( 5 of 26 ) in group A and B , respectively ( p = 0.052 ) . Median time to the first recurrence was 8 months in group A and 7 months in group B ( p = 0.12 ) . CONCLUSIONS The present study showed no statistically significant difference in terms of recurrence rate and median time to first recurrence between intermediate or high-risk patients with NMIBC who were treated with early single dose instillation of MMC plus delayed BCG and those who were treated with only BCG BACKGROUND Bacillus Calmette-Guérin ( BCG ) and epirubicin have both been shown to be effective in the treatment of superficial bladder cancer . We studied whether the alternating combination of these agents could improve the efficacy with tolerable side-effects in the treatment of high-risk superficial bladder tumors . METHODS Forty-one patients with high-risk superficial bladder transitional carcinoma were included in this study . Twenty-one patients were r and omized into the BCG group and 20 patients were treated with sequential BCG and epirubicin . The patients were followed for 9 - 24 months ( mean 18 months ) . Recurrence rates , median time to the first recurrence , progression rate and complications were compared . RESULTS Fifteen percent of the patients in the BCG and epirubicin group and 19 % of the patients in the BCG alone group developed tumor recurrence . Tumor progression was observed in 4.7 % and 10 % in the BCG/epirubicin group and the BCG alone group , respectively . Median time to first recurrence was 11 months for the BCG/epirubicin group and 16 months for the BCG group ( P > 0.05 ) . Three patients in the BCG/epirubicin treatment group developed serious side-effects , which necessitated antituberculosis treatment . CONCLUSION Because the efficacy of combination was no better than the st and ard treatment and the alternating combination seemed to be related to a higher incidence of side-effects , this study albeit small , does not recommend combination therapy of BCG and epirubicin in high risk patients with superficial bladder cancer PURPOSE We attempted to prove if alternating chemoprophylactic and immunoprophylactic instillations improved efficacy and decreased toxicity in patients with recurrent superficial bladder cancer . MATERIAL S AND METHODS A total of 188 patients with rapidly recurring stage Ta or T1 cancer was r and omly treated with mitomycin C ( group 1 ) or alternating mitomycin C and Pasteur strain bacillus Calmette-Guerin ( BCG ) instillations ( group 2 ) for 2 years . Mean followup was 34 months . RESULTS Median times to initial recurrence were 12 months in group 1 and 7 months in group 2 ( p = 0.976 ) , and treatment failed in 21.5 % and 18.9 % , respectively . Recurrence rates during the instillation period were 1.01 in group 1 and 0.86 in group 2 ( p = 0.376 ) . There was no difference in the disease-free interval between the 2 groups ( p = 0.976 ) . Instillations were discontinued because of adverse effects in 6 cases ( 6 % ) in both groups . CONCLUSIONS Efficacy of alternating mitomycin C and BCG was equal to mitomycin C monotherapy , and both methods were effective in prophylaxis of recurrent papillary bladder cancer . Less toxicity occurred in the alternating treatment group compared to earlier BCG monotherapy results To examine whether intravesical instillation of low-dose bacillus Calmette-Guérin ( BCG ) therapy is effective with low toxicity , we review ed data for 111 patients with superficial bladder cancer ( stages Ta and T1 ) . Among them , 74 received the BCG treatment for prophylaxis of intravesical recurrence after transurethral resection , and the remaining 37 therapeutically for Ta or T1 tumours . The patients were divided into two groups by instillation dose of BCG ( Tokyo 172 strain ) : 40 mg ( n=55 ) and 80 mg ( n=56 ) , and statistically compared for recurrence , antitumour effect and toxicity . The mean instillations were done 8.4 times in the 40 mg dose group and 8.6 times in the 80 mg dose group . Among the 74 patients with BCG therapy for prophylaxis those with a previous episode of bladder cancer treatment ( n=47 ) experienced a significantly ( p=0.006 ) shorter recurrence-free interval than those with no episode ( n=27 ) . Among 47 patients with a previous treatment episode , those receiving the 80 mg dose demonstrated a significantly longer recurrence-free interval than those given the 40 mg dose ( p=0.03 ) . Among the 27 patients without previous treatment no significant difference in recurrence-free intervals was found between the two dose groups . Univariate and multivariate aalyses using Cox 's proportional hazards model confirmed the above findings . The drecurrence index was also significantly reduced after BCG therapy in the 80 mg and 40 mg groups and similar antitumour effects for Ta or T1 tumours were observed in the two dose groups . The degree of toxicity due to BCG therapy was significantly ( p=0.02 ) lower with the 40 mg dose . The present study suggests that ( 1 ) a 40 mg BCG low-dose ( Tokyo 172 strain ) regimen is useful for preventing recurrence , with sufficient therapeutic efficacy and low frequency of toxicity , among patients without a previous treatment , and ( 2 ) prophylactic effects with the 80 mg dose regimen are much superior for previous treatment cases OBJECTIVE The primary aim was to search for lower doses of Bacillus Calmette-Guerin ( BCG ) that are effective and have lower toxicity . METHODS A low dose of BCG 27 mg was compared with BCG 13.5 mg , using mitomycin C ( MMC ) 30 mg as the third arm of comparison . A total of 430 patients with intermediate-risk superficial bladder cancer were r and omised into three groups . Instillations were repeated once a week for 6 wk followed by another six instillations given once every 2 wk during 12 wk . RESULTS There was a significantly longer disease-free interval for BCG 27 mg versus MMC 30 mg ( p=0.006 ) . There were no statistically significant differences between BCG 27 mg and BCG 13.5 mg ( p=0.165 ) or between BCG 13.5 mg and MMC 30 mg ( p=0.183 ) . Cox proportional hazards regression showed that disease-free interval in the multivariate analysis was significantly better for primary disease and treatment with BCG 27 mg . There were no significant differences among the three groups with regards to time to progression and cancer-specific survival time . Local and systemic toxicity were higher in both BCG treatment groups . CONCLUSIONS One third of the st and ard dose , BCG 27 mg , seems to be the minimum effective dose as adjuvant treatment for intermediate-risk superficial bladder cancer , being more effective than MMC 30 mg . One sixth of the st and ard dose , BCG 13.5 mg , has the same efficacy as MMC 30 mg but it is more toxic PURPOSE Intravesical instillations of bacillus Calmette-Guerin have demonstrated satisfactory results in the treatment of vesical carcinoma in situ and high grade superficial bladder tumors . We design ed a protocol to evaluate the decrease in tumor recurrence with maintenance therapy . MATERIAL S AND METHODS Between June  
    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: BACKGROUND The optimal dose and duration of intravesical bacillus Calmette-Guérin ( BCG ) in the treatment of non-muscle-invasive bladder cancer ( NMIBC ) are controversial . OBJECTIVE To determine if a one-third dose ( 1/3D ) is not inferior to the full dose ( FD ) , if 1 yr of maintenance is not inferior to 3 yr of maintenance , and if 1/3D and 1 yr of maintenance are associated with less toxicity . DESIGN , SETTING , AND PARTICIPANTS After transurethral resection , intermediate- and high-risk NMIBC patients were r and omized to one of four BCG groups :  1/3D-1 yr , 1/3D-3 yr , FD-1 yr , and FD-3 yr . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The trial was design ed as a noninferiority study with the null hypothesis of a 10 % decrease in the disease-free rate at 5 yr . Times to events were estimated using cumulative incidence functions and compared using the Cox proportional hazards regression model . RESULTS AND LIMITATIONS In an intention-to-treat analysis of 1355 patients with a median follow-up of 7.1 yr , there were no significant differences in toxicity between 1/3D and FD . The null hypotheses of inferiority of the disease-free interval for both 1/3D and 1 yr could not be rejected . We found that 1/3D-1 yr is suboptimal compared with FD-3 yr ( hazard ratio [ HR ] : 0.75 ; 95 % confidence interval [ CI ] , 0.59 - 0.94 ; p=0.01 ) . Intermediate-risk patients treated with FD do not benefit from an additional 2 yr of BCG . In high-risk patients , 3 yr is associated with a reduction in recurrence ( HR : 1.61 ; 95 % CI , 1.13 - 2.30 ; p=0.009 ) but only when given at FD . There were no differences in progression or survival . CONCLUSIONS There were no differences in toxicity between 1/3D and FD . Intermediate-risk patients should be treated with FD-1 yr . In high-risk patients , FD-3 yr reduces recurrences as compared with FD-1 yr but not progressions or deaths . The benefit of the two additional years of maintenance should be weighed against its added costs and inconvenience . TRIAL REGISTRATION This study was registered at Clinical Trials.gov , number NCT00002990 ; http:// clinical trials.gov/ct2/show/record/NCT00002990 BACKGROUND Intravesical instillation of bacillus Calmette-Guérin ( BCG ) is the most efficient strategy for prophylaxis of superficial bladder cancer recurrence .  Adverse effects of BCG are major obstacles , but the reduction of BCG dose could minimize these effects . The efficacy and adverse effects of half-dose ( 40 mg ) BCG , Tokyo 172 strain , were prospect ively evaluated . METHODS A total of 93 patients with superficial bladder cancer ( pTa or pT1 ) were sequentially assigned to receive either 40 or 80 mg of BCG after transurethral resection . BCG was administered weekly for 6 weeks postoperatively . Eighty patients observed longer than 12 months after BCG therapy ( 41 , 40 mg group ; 39 , 80 mg group ) were analyzed . RESULTS BCG therapy course was completed in 71 patients . Tumor recurrence was recognized in 11 of 40 patients in the 40 mg group and in 5 of 31 patients in the 80 mg group . There was no significant difference in tumor recurrence rate between the two groups ( P = 0.547 ) . BCG therapy was withdrawn in 1 patient in the 40 mg group and in 8 patients in the 80 mg-group because of BCG-related adverse effects . The morbidity of BCG-related toxicity was significantly higher in the 80 mg group . CONCLUSION Half-dose of BCG Tokyo 172 strain had a similar efficacy and its toxicity was significantly lower compared to the st and ard dose . Thus , half-dose of this strain might be suitable , at least for initial BCG therapy , for the prophylaxis of bladder cancer recurrence . Further study would be necessary to clarify the efficacy of low-dose instillation in high-risk patients PURPOSE We evaluated the efficacy of perioperative mitomycin C ( MMC ) instillation to improve subsequent  bacillus Calmette-Guérin ( BCG )  instillation efficacy in intermediate and high risk patients with non-muscle invasive bladder cancer ( NMIBC ) . MATERIAL S AND METHODS From November 2004 to May 2006 , 51 patients with intermediate or high risk NMIBC were enrolled in this prospect i ve r and omized trial . In group A , patients were treated with perioperative MMC ( 40 mg MMC in 40 mL saline was administered within 6 hours of surgery ) followed by delayed ( at least 15 days from surgery ) BCG instillations ( once a week for 6 weeks , 5 x 108 colony-forming units in 50 mL saline ) . Patients in group B were treated with delayed BCG instillations alone . The primary end points were recurrence-free interval and recurrence rate . RESULTS There were 25 and 26 patients in groups A and B , respectively . Median follow-up was 41.3 months ( range 8 to 64 ) in group A and 40.9 months ( range 6 to 68 ) in group B. Recurrence rate was 36 % ( 9 of 25 ) and 19.3 % ( 5 of 26 ) in group A and B , respectively ( p = 0.052 ) . Median time to the first recurrence was 8 months in group A and 7 months in group B ( p = 0.12 ) . CONCLUSIONS The present study showed no statistically significant difference in terms of recurrence rate and median time to first recurrence between intermediate or high-risk patients with NMIBC who were treated with early single dose instillation of MMC plus delayed BCG and those who were treated with only BCG BACKGROUND Bacillus Calmette-Guérin ( BCG ) and epirubicin have both been shown to be effective in the treatment of superficial bladder cancer . We studied whether the alternating combination of these agents could improve the efficacy with tolerable side-effects in the treatment of high-risk superficial bladder tumors . METHODS Forty-one patients with high-risk superficial bladder transitional carcinoma were included in this study . Twenty-one patients were r and omized into the BCG group and 20 patients were treated with sequential BCG and epirubicin . The patients were followed for 9 - 24 months ( mean 18 months ) . Recurrence rates , median time to the first recurrence , progression rate and complications were compared . RESULTS Fifteen percent of the patients in the BCG and epirubicin group and 19 % of the patients in the BCG alone group developed tumor recurrence . Tumor progression was observed in 4.7 % and 10 % in the BCG/epirubicin group and the BCG alone group , respectively . Median time to first recurrence was 11 months for the BCG/epirubicin group and 16 months for the BCG group ( P > 0.05 ) . Three patients in the BCG/epirubicin treatment group developed serious side-effects , which necessitated antituberculosis treatment . CONCLUSION Because the efficacy of combination was no better than the st and ard treatment and the alternating combination seemed to be related to a higher incidence of side-effects , this study albeit small , does not recommend combination therapy of BCG and epirubicin in high risk patients with superficial bladder cancer PURPOSE We attempted to prove if alternating chemoprophylactic and immunoprophylactic instillations improved efficacy and decreased toxicity in patients with recurrent superficial bladder cancer . MATERIAL S AND METHODS A total of 188 patients with rapidly recurring stage Ta or T1 cancer was r and omly treated with mitomycin C ( group 1 ) or alternating mitomycin C and Pasteur strain bacillus Calmette-Guerin ( BCG ) instillations ( group 2 ) for 2 years . Mean followup was 34 months . RESULTS Median times to initial recurrence were 12 months in group 1 and 7 months in group 2 ( p = 0.976 ) , and treatment failed in 21.5 % and 18.9 % , respectively . Recurrence rates during the instillation period were 1.01 in group 1 and 0.86 in group 2 ( p = 0.376 ) . There was no difference in the disease-free interval between the 2 groups ( p = 0.976 ) . Instillations were discontinued because of adverse effects in 6 cases ( 6 % ) in both groups . CONCLUSIONS Efficacy of alternating mitomycin C and BCG was equal to mitomycin C monotherapy , and both methods were effective in prophylaxis of recurrent papillary bladder cancer . Less toxicity occurred in the alternating treatment group compared to earlier BCG monotherapy results To examine whether intravesical instillation of low-dose bacillus Calmette-Guérin ( BCG ) therapy is effective with low toxicity , we review ed data for 111 patients with superficial bladder cancer ( stages Ta and T1 ) . Among them , 74 received the BCG treatment for prophylaxis of intravesical recurrence after transurethral resection , and the remaining 37 therapeutically for Ta or T1 tumours . The patients were divided into two groups by instillation dose of BCG ( Tokyo 172 strain ) : 40 mg ( n=55 ) and 80 mg ( n=56 ) , and statistically compared for recurrence , antitumour effect and toxicity . The mean instillations were done 8.4 times in the 40 mg dose group and 8.6 times in the 80 mg dose group . Among the 74 patients with BCG therapy for prophylaxis those with a previous episode of bladder cancer treatment ( n=47 ) experienced a significantly ( p=0.006 ) shorter recurrence-free interval than those with no episode ( n=27 ) . Among 47 patients with a previous treatment episode , those receiving the 80 mg dose demonstrated a significantly longer recurrence-free interval than those given the 40 mg dose ( p=0.03 ) . Among the 27 patients without previous treatment no significant difference in recurrence-free intervals was found between the two dose groups . Univariate and multivariate aalyses using Cox 's proportional hazards model confirmed the above findings . The drecurrence index was also significantly reduced after BCG therapy in the 80 mg and 40 mg groups and similar antitumour effects for Ta or T1 tumours were observed in the two dose groups . The degree of toxicity due to BCG therapy was significantly ( p=0.02 ) lower with the 40 mg dose . The present study suggests that ( 1 ) a 40 mg BCG low-dose ( Tokyo 172 strain ) regimen is useful for preventing recurrence , with sufficient therapeutic efficacy and low frequency of toxicity , among patients without a previous treatment , and ( 2 ) prophylactic effects with the 80 mg dose regimen are much superior for previous treatment cases OBJECTIVE The primary aim was to search for lower doses of Bacillus Calmette-Guerin ( BCG ) that are effective and have lower toxicity . METHODS A low dose of BCG 27 mg was compared with BCG 13.5 mg , using mitomycin C ( MMC ) 30 mg as the third arm of comparison . A total of 430 patients with intermediate-risk superficial bladder cancer were r and omised into three groups . Instillations were repeated once a week for 6 wk followed by another six instillations given once every 2 wk during 12 wk . RESULTS There was a significantly longer disease-free interval for BCG 27 mg versus MMC 30 mg ( p=0.006 ) . There were no statistically significant differences between BCG 27 mg and BCG 13.5 mg ( p=0.165 ) or between BCG 13.5 mg and MMC 30 mg ( p=0.183 ) . Cox proportional hazards regression showed that disease-free interval in the multivariate analysis was significantly better for primary disease and treatment with BCG 27 mg . There were no significant differences among the three groups with regards to time to progression and cancer-specific survival time . Local and systemic toxicity were higher in both BCG treatment groups . CONCLUSIONS One third of the st and ard dose , BCG 27 mg , seems to be the minimum effective dose as adjuvant treatment for intermediate-risk superficial bladder cancer , being more effective than MMC 30 mg . One sixth of the st and ard dose , BCG 13.5 mg , has the same efficacy as MMC 30 mg but it is more toxic PURPOSE Intravesical instillations of bacillus Calmette-Guerin have demonstrated satisfactory results in the treatment of vesical carcinoma in situ and high grade superficial bladder tumors . We design ed a protocol to evaluate the decrease in tumor recurrence with maintenance therapy . MATERIAL S AND METHODS Between June  
    Output:
    