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 purpose of the study was to evaluate the benefit of adjuvant chemotherapy ( AC ) versus surgery alone in patients with muscle-invasive bladder cancer ( MIBC ) . PATIENTS AND METHODS One hundred and ninety-four patients with pT2G3 , pT3 - 4 , N0 - 2 transitional cell bladder carcinoma were r and omly allocated to control ( 92 patients ) or to four courses of AC ( 102 patients ) . These latter patients were further r and omly assigned to receive gemcitabine 1000 mg/m(2 ) days 1 , 8 and 15 and cisplatin 70 mg/m(2 ) day 2 or gemcitabine as above plus cisplatin 70 mg/m(2 ) day 15 , every 28 days . RESULTS At a median follow-up of 35 months , the 5-year overall survival ( OS ) was 48.5 % , with no difference between the two arms [ P = 0.24 , hazard ratio ( HR ) 1.29 , 95 % confidence interval ( CI ) 0.84 - 1.99 ] . Mortality hazard was significantly correlated with Nodes ( N ) and Tumor ( T ) stage . The control and AC arms had comparable disease-free survival ( 42.3 % and 37.2 % , respectively ; P = 0.70 , HR 1.08 , 95 % CI 0.73 - 1.59 ) . Only 62 % of patients received the planned cycles . A significant higher incidence of thrombocytopenia was observed in patients receiving cisplatin on day 2 ( P = 0.006 ) . A similar global quality of life was observed in the two arms . CONCLUSION The study was underpowered to demonstrate that AC with cisplatin and gemcitabine improves OS and disease-free survival in patients with MIBC BACKGROUND AND PURPOSE To determine the feasibility , toxicity , and clinical effectiveness of concurrent weekly cisplatin chemotherapy in conjunction with definitive radiation in the treatment of localised muscle invasive bladder cancer . PATIENTS AND METHODS In January 1997 the Trans Tasman Radiation Oncology Group embarked on a Phase II study ( TROG 97.01 ) of weekly cisplatin ( 35 mg/m(2 ) x 7 doses ) plus radiation to a dose of 63 Gy over 7 weeks . Following an interim toxicity analysis , the dose intensity of cisplatin was reduced to 6 cycles and the radiation schedule changed to 64 Gy over 6.5 weeks leading to the second study ( TROG 99.06 ) . A total of 113 patients were enrolled . RESULTS Acute grade 3 urinary toxicity occurred in 23 % of the patients . Acute grade 4 pelvic toxicity was not seen . Thirty-eight patients ( 33 % ) experienced grade 3 or 4 cisplatin related toxicities with 15 patients ( 12 % ) requiring significant dose modification . The reduced dose intensity in Study 99.06 improved tolerability . Incidence of significant late morbidity was low ( 6 % ) . Seventy-nine patients ( 70 % ) achieved complete remission at the 6 month cystoscopic assessment . Local invasive recurrence was seen in 11 of the 79 patients ( 14 % ) . In 18 patients ( 16 % ) isolated superficial TCC/CIS were detected ( 6 months and beyond ) . The local control rate was 45 % with a functional bladder being retained in 69 of the 113 patients ( 61 % ) . RFS and DSS at 5 years were 33 % and 50 % , respectively . CONCLUSION Our two sequential Phase II studies have shown that concurrent chemoradiation using weekly cisplatin in the management of localised invasive bladder TCC is feasible and reasonably well tolerated . This approach is currently being investigated further in a r and omised study PURPOSE St and ard treatment for muscle invasive transitional cell cancer of the bladder is radical cystectomy . Despite careful staging , the majority of cancers with regional lymph node involvement and /or invasion to adjacent organs eventually recur . We investigated the benefit of chemotherapy with cisplatin , methotrexate and vinblastine ( CMV ) after radical cystectomy . MATERIAL S AND METHODS A prospect i ve trial was done in which patients were r and omized after cystectomy to receive either 4 cycles of CMV chemotherapy or observation .  At relapse , patients were treated with st and ard CMV chemotherapy for metastatic disease at our institution . RESULTS Of 55 patients who entered this trial 1 was ineligible and in 4 it is too soon to be evaluated . Of the 50 evaluable patients 25 were r and omized to receive adjuvant CMV chemotherapy and 25 were observed . In the CMV arm 12 ( 48 % ) and in the observation arm 5 ( 25 % ) never had recurrence . With a median followup of 62 months and no patient with less than 2 years of followup , the freedom from progression in the adjuvant chemotherapy group was superior to that in the observation group ( median 37 versus 12 months , respectively , p = 0.01 ) . Median survival in the adjuvant group was 63 months compared to 36 months for the observation group . Surprisingly , some cases with relapse could be salvaged with CMV chemotherapy , perhaps contributing to this lack of difference in overall survival ( p = 0.32 ) . CONCLUSIONS Treatment with CMV chemotherapy after radical cystectomy is an acceptable approach in patients with stages p3b and p4N0 or N1 transitional cell carcinoma of the bladder . Further studies must be performed to determine whether these results can be extrapolated to patients with more limited disease ( stages p2 and p3a ) who are currently treated with radical cystectomy or definitive irradiation PURPOSE We evaluated the feasibility and efficacy of the organ preserving strategy of intra-arterial cisplatin and concurrent radiotherapy for localized bladder cancer . MATERIAL S AND METHODS Bladder preservation has been pursued over the decades in treatment regimens featuring radiotherapy alone or in conjunction with single or multiagent chemotherapy . The chemotherapy has consisted almost exclusively of intravenously administered drugs . There are theoretical and clinical data demonstrating a higher concentration of cisplatin within tumors following intra-arterial as opposed to intravenous delivery . This study was performed to evaluate whether this increased concentration would enhance radiosensitization and thereby increase the success of bladder preservation . RESULTS We report on our prospect ively collected experience during 15 years of treating 200 patients with localized bladder cancer using this regimen of 3 courses of intra-arterial cisplatin integrated with pelvic radiotherapy  and reserving cystectomy for salvage as required . We report on the efficacy in terms of complete response rate , ultimate tumor-free bladder preservation , overall survival and patterns of failure . We detail the acute and chronic toxicity observed to date . CONCLUSIONS This strategy has result ed in a durable high complete response rate and overall tumor-free bladder preservation rate of 75 % while maintaining a survival comparable to that achieved with cystectomy . These results corroborate the hypothesis that intra-arterial administration of cisplatin enhances radiosensitization during pelvic radiotherapy BACKGROUND We report the outcome of radical cystectomy for patients with invasive bladder cancer , who did not have regional lymph node or distant metastases , at 21 hospitals . METHODS Retrospective , non-r and omized , multi-institutional pooled data were analyzed to evaluate outcomes of patients who received radical cystectomy . Between 1991 and 1995 , 518 patients with invasive bladder cancer were treated with radical cystectomy at 21 hospitals . Of these , 250 patients ( 48.3 % ) received some type of neoadjuvant and /or adjuvant therapy depending on the treatment policy of each hospital . RESULTS The median follow-up period was 4.4 years , ranging from 0.1 to 11.4 years . The 5-year overall survival rate was 58 % for all 518 patients . The 5-year overall survival rates for patients with clinical T2N0M0 , T3N0M0 and T4N0M0 were 67 % , 52 % and 38 % , respectively . The patients with pT1 or lower stage , pT2 , pT3 and pT4 disease without lymph node metastasis had 5-year overall survivals of 81 % , 74 % , 47 % and 38 % , respectively . The patients who were node positive had the worst prognosis , with a 30 % overall survival rate at 5 years . Neoadjuvant or adjuvant chemotherapy did not provide a significant survival advantage , although adjuvant chemotherapy improved the 5-year overall survival in patients with pathologically proven lymph node metastasis . CONCLUSIONS The current retrospective study showed that radical cystectomy provided an overall survival equivalent to studies reported previously , but surgery alone had no more potential to prolong survival of patients with invasive cancer . Therefore , a large-scale r and omized study on adjuvant treatment as well as development of new strategies will be needed to improve the outcome for patients with invasive bladder cancer We conducted a phase I/II study investigating synchronous chemoradiotherapy with mitomycin C and infusional 5-fluorouracil ( 5-FU ) in muscle invasive bladder cancer . Early dose escalation results were previously published . We report the long-term toxicity and efficacy results with the optimised regimen . Patients with muscle invasive bladder cancer with glomerular filtration rate > 25 ml min−1 were eligible .  Mitomycin ( 12 mg m−2 on day 1 only ) and infusional 5-FU ( 500 mg m−2 day−1 ) for 5 days were administered during weeks 1 and 4 of radiotherapy of 55 Gy in 20 fractions . A total of 41 patients were enrolled , median age was 68 years , 33 were male and eight female patients . Out of the 41 patients , 20 ( 49 % ) had hydronephrosis at presentation and 25 ( 62 % ) had T3b or T4 disease . Four patients experienced Grade III thrombocytopenia and three patients had Grade III neutropenia . There were no episodes of febrile neutropenia . Four patients experienced Grade III diarrhoea and 1 Grade III urgency and dysuria . Six patients did not undergo cystoscopic evaluation due to early metastatic spread although there was no clinical suggestion of bladder failure . In all , out of 35 evaluable patients , 25 ( 71 % ) had macroscopic complete response at 3-month cystoscopy , and biopsy confirmed in 24 out of 25 . A total of 16 ( 39 % ) patients remain alive with a median follow-up of 50.7 ( range 23.5–68.8 ) months , 14 with a functioning bladder with no reported long-term treatment-related bladder or bowel toxicity . Five out of 41 patients have undergone salvage cystectomy : two for persistent CIS , two T1 and one muscle invasive recurrence . Four patients have received intravesical chemotherapy , of whom two remain alive with a functioning bladder . Overall 12- , 24- and 60-month ( m ) survival rates were 68 , 49 and 36 % . Local and distant progression free rates were 82 and 86 % at 12-m and 79 and 75 % at 24-m . Organ preservation using multimodality therapy is feasible and safe , even in patients with poor renal reserve , and does not compromise salvage therapies . A national phase III trial BC2001 ( www.bc2001.org.uk ) exploring the effects of synchronous chemoradiotherapy with this regimen is currently recruiting OBJECTIVES To determine the long-term results of a bladder-sparing approach in the treatment of muscle-invasive bladder cancer . METHODS Ninety-four patients with invasive transitional cell carcinoma of the bladder were treated by transurethral resection followed by 2 or 3 cycles of cisplatin-based chemotherapy . Patients were then treated with 6480 cGy of radiation in 49 patients , segmental cystectomy in 8 , or surveillance only in 7 . Patients who failed to respond to chemotherapy or radiation therapy , or who developed recurrent muscle-invasive disease in follow-up , underwent salvage cystectomy . Patients were then carefully followed for a median follow-up of more than 5 years . RESULTS After initial therapy , 53 patients ( 56 % ) were alive with their bladder preserved . Thirty of those 53 ( 57 % ) developed a local recurrence in follow-up . After a median follow-up of more than 5 years , the ultimate relapse-free survival is 49 % ( Stage T2 , 84 % ; T3 , 53 % ; and T4 , 11 % ; P < 0.01 ) . Of all patients enrolled , 53 % had bladder preservation ; however , of the currently surviving patients , 16 of 39 ( 41 % ) have their bladders intact ( T2 , 50 % ; T3 , 37 % ; T4 , 0 % ) . Only 18 % of the initially enrolled population is alive with a preserved bladder . 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: BACKGROUND The purpose of the study was to evaluate the benefit of adjuvant chemotherapy ( AC ) versus surgery alone in patients with muscle-invasive bladder cancer ( MIBC ) . PATIENTS AND METHODS One hundred and ninety-four patients with pT2G3 , pT3 - 4 , N0 - 2 transitional cell bladder carcinoma were r and omly allocated to control ( 92 patients ) or to four courses of AC ( 102 patients ) . These latter patients were further r and omly assigned to receive gemcitabine 1000 mg/m(2 ) days 1 , 8 and 15 and cisplatin 70 mg/m(2 ) day 2 or gemcitabine as above plus cisplatin 70 mg/m(2 ) day 15 , every 28 days . RESULTS At a median follow-up of 35 months , the 5-year overall survival ( OS ) was 48.5 % , with no difference between the two arms [ P = 0.24 , hazard ratio ( HR ) 1.29 , 95 % confidence interval ( CI ) 0.84 - 1.99 ] . Mortality hazard was significantly correlated with Nodes ( N ) and Tumor ( T ) stage . The control and AC arms had comparable disease-free survival ( 42.3 % and 37.2 % , respectively ; P = 0.70 , HR 1.08 , 95 % CI 0.73 - 1.59 ) . Only 62 % of patients received the planned cycles . A significant higher incidence of thrombocytopenia was observed in patients receiving cisplatin on day 2 ( P = 0.006 ) . A similar global quality of life was observed in the two arms . CONCLUSION The study was underpowered to demonstrate that AC with cisplatin and gemcitabine improves OS and disease-free survival in patients with MIBC BACKGROUND AND PURPOSE To determine the feasibility , toxicity , and clinical effectiveness of concurrent weekly cisplatin chemotherapy in conjunction with definitive radiation in the treatment of localised muscle invasive bladder cancer . PATIENTS AND METHODS In January 1997 the Trans Tasman Radiation Oncology Group embarked on a Phase II study ( TROG 97.01 ) of weekly cisplatin ( 35 mg/m(2 ) x 7 doses ) plus radiation to a dose of 63 Gy over 7 weeks . Following an interim toxicity analysis , the dose intensity of cisplatin was reduced to 6 cycles and the radiation schedule changed to 64 Gy over 6.5 weeks leading to the second study ( TROG 99.06 ) . A total of 113 patients were enrolled . RESULTS Acute grade 3 urinary toxicity occurred in 23 % of the patients . Acute grade 4 pelvic toxicity was not seen . Thirty-eight patients ( 33 % ) experienced grade 3 or 4 cisplatin related toxicities with 15 patients ( 12 % ) requiring significant dose modification . The reduced dose intensity in Study 99.06 improved tolerability . Incidence of significant late morbidity was low ( 6 % ) . Seventy-nine patients ( 70 % ) achieved complete remission at the 6 month cystoscopic assessment . Local invasive recurrence was seen in 11 of the 79 patients ( 14 % ) . In 18 patients ( 16 % ) isolated superficial TCC/CIS were detected ( 6 months and beyond ) . The local control rate was 45 % with a functional bladder being retained in 69 of the 113 patients ( 61 % ) . RFS and DSS at 5 years were 33 % and 50 % , respectively . CONCLUSION Our two sequential Phase II studies have shown that concurrent chemoradiation using weekly cisplatin in the management of localised invasive bladder TCC is feasible and reasonably well tolerated . This approach is currently being investigated further in a r and omised study PURPOSE St and ard treatment for muscle invasive transitional cell cancer of the bladder is radical cystectomy . Despite careful staging , the majority of cancers with regional lymph node involvement and /or invasion to adjacent organs eventually recur . We investigated the benefit of chemotherapy with cisplatin , methotrexate and vinblastine ( CMV ) after radical cystectomy . MATERIAL S AND METHODS A prospect i ve trial was done in which patients were r and omized after cystectomy to receive either 4 cycles of CMV chemotherapy or observation .  At relapse , patients were treated with st and ard CMV chemotherapy for metastatic disease at our institution . RESULTS Of 55 patients who entered this trial 1 was ineligible and in 4 it is too soon to be evaluated . Of the 50 evaluable patients 25 were r and omized to receive adjuvant CMV chemotherapy and 25 were observed . In the CMV arm 12 ( 48 % ) and in the observation arm 5 ( 25 % ) never had recurrence . With a median followup of 62 months and no patient with less than 2 years of followup , the freedom from progression in the adjuvant chemotherapy group was superior to that in the observation group ( median 37 versus 12 months , respectively , p = 0.01 ) . Median survival in the adjuvant group was 63 months compared to 36 months for the observation group . Surprisingly , some cases with relapse could be salvaged with CMV chemotherapy , perhaps contributing to this lack of difference in overall survival ( p = 0.32 ) . CONCLUSIONS Treatment with CMV chemotherapy after radical cystectomy is an acceptable approach in patients with stages p3b and p4N0 or N1 transitional cell carcinoma of the bladder . Further studies must be performed to determine whether these results can be extrapolated to patients with more limited disease ( stages p2 and p3a ) who are currently treated with radical cystectomy or definitive irradiation PURPOSE We evaluated the feasibility and efficacy of the organ preserving strategy of intra-arterial cisplatin and concurrent radiotherapy for localized bladder cancer . MATERIAL S AND METHODS Bladder preservation has been pursued over the decades in treatment regimens featuring radiotherapy alone or in conjunction with single or multiagent chemotherapy . The chemotherapy has consisted almost exclusively of intravenously administered drugs . There are theoretical and clinical data demonstrating a higher concentration of cisplatin within tumors following intra-arterial as opposed to intravenous delivery . This study was performed to evaluate whether this increased concentration would enhance radiosensitization and thereby increase the success of bladder preservation . RESULTS We report on our prospect ively collected experience during 15 years of treating 200 patients with localized bladder cancer using this regimen of 3 courses of intra-arterial cisplatin integrated with pelvic radiotherapy  and reserving cystectomy for salvage as required . We report on the efficacy in terms of complete response rate , ultimate tumor-free bladder preservation , overall survival and patterns of failure . We detail the acute and chronic toxicity observed to date . CONCLUSIONS This strategy has result ed in a durable high complete response rate and overall tumor-free bladder preservation rate of 75 % while maintaining a survival comparable to that achieved with cystectomy . These results corroborate the hypothesis that intra-arterial administration of cisplatin enhances radiosensitization during pelvic radiotherapy BACKGROUND We report the outcome of radical cystectomy for patients with invasive bladder cancer , who did not have regional lymph node or distant metastases , at 21 hospitals . METHODS Retrospective , non-r and omized , multi-institutional pooled data were analyzed to evaluate outcomes of patients who received radical cystectomy . Between 1991 and 1995 , 518 patients with invasive bladder cancer were treated with radical cystectomy at 21 hospitals . Of these , 250 patients ( 48.3 % ) received some type of neoadjuvant and /or adjuvant therapy depending on the treatment policy of each hospital . RESULTS The median follow-up period was 4.4 years , ranging from 0.1 to 11.4 years . The 5-year overall survival rate was 58 % for all 518 patients . The 5-year overall survival rates for patients with clinical T2N0M0 , T3N0M0 and T4N0M0 were 67 % , 52 % and 38 % , respectively . The patients with pT1 or lower stage , pT2 , pT3 and pT4 disease without lymph node metastasis had 5-year overall survivals of 81 % , 74 % , 47 % and 38 % , respectively . The patients who were node positive had the worst prognosis , with a 30 % overall survival rate at 5 years . Neoadjuvant or adjuvant chemotherapy did not provide a significant survival advantage , although adjuvant chemotherapy improved the 5-year overall survival in patients with pathologically proven lymph node metastasis . CONCLUSIONS The current retrospective study showed that radical cystectomy provided an overall survival equivalent to studies reported previously , but surgery alone had no more potential to prolong survival of patients with invasive cancer . Therefore , a large-scale r and omized study on adjuvant treatment as well as development of new strategies will be needed to improve the outcome for patients with invasive bladder cancer We conducted a phase I/II study investigating synchronous chemoradiotherapy with mitomycin C and infusional 5-fluorouracil ( 5-FU ) in muscle invasive bladder cancer . Early dose escalation results were previously published . We report the long-term toxicity and efficacy results with the optimised regimen . Patients with muscle invasive bladder cancer with glomerular filtration rate > 25 ml min−1 were eligible .  Mitomycin ( 12 mg m−2 on day 1 only ) and infusional 5-FU ( 500 mg m−2 day−1 ) for 5 days were administered during weeks 1 and 4 of radiotherapy of 55 Gy in 20 fractions . A total of 41 patients were enrolled , median age was 68 years , 33 were male and eight female patients . Out of the 41 patients , 20 ( 49 % ) had hydronephrosis at presentation and 25 ( 62 % ) had T3b or T4 disease . Four patients experienced Grade III thrombocytopenia and three patients had Grade III neutropenia . There were no episodes of febrile neutropenia . Four patients experienced Grade III diarrhoea and 1 Grade III urgency and dysuria . Six patients did not undergo cystoscopic evaluation due to early metastatic spread although there was no clinical suggestion of bladder failure . In all , out of 35 evaluable patients , 25 ( 71 % ) had macroscopic complete response at 3-month cystoscopy , and biopsy confirmed in 24 out of 25 . A total of 16 ( 39 % ) patients remain alive with a median follow-up of 50.7 ( range 23.5–68.8 ) months , 14 with a functioning bladder with no reported long-term treatment-related bladder or bowel toxicity . Five out of 41 patients have undergone salvage cystectomy : two for persistent CIS , two T1 and one muscle invasive recurrence . Four patients have received intravesical chemotherapy , of whom two remain alive with a functioning bladder . Overall 12- , 24- and 60-month ( m ) survival rates were 68 , 49 and 36 % . Local and distant progression free rates were 82 and 86 % at 12-m and 79 and 75 % at 24-m . Organ preservation using multimodality therapy is feasible and safe , even in patients with poor renal reserve , and does not compromise salvage therapies . A national phase III trial BC2001 ( www.bc2001.org.uk ) exploring the effects of synchronous chemoradiotherapy with this regimen is currently recruiting OBJECTIVES To determine the long-term results of a bladder-sparing approach in the treatment of muscle-invasive bladder cancer . METHODS Ninety-four patients with invasive transitional cell carcinoma of the bladder were treated by transurethral resection followed by 2 or 3 cycles of cisplatin-based chemotherapy . Patients were then treated with 6480 cGy of radiation in 49 patients , segmental cystectomy in 8 , or surveillance only in 7 . Patients who failed to respond to chemotherapy or radiation therapy , or who developed recurrent muscle-invasive disease in follow-up , underwent salvage cystectomy . Patients were then carefully followed for a median follow-up of more than 5 years . RESULTS After initial therapy , 53 patients ( 56 % ) were alive with their bladder preserved . Thirty of those 53 ( 57 % ) developed a local recurrence in follow-up . After a median follow-up of more than 5 years , the ultimate relapse-free survival is 49 % ( Stage T2 , 84 % ; T3 , 53 % ; and T4 , 11 % ; P < 0.01 ) . Of all patients enrolled , 53 % had bladder preservation ; however , of the currently surviving patients , 16 of 39 ( 41 % ) have their bladders intact ( T2 , 50 % ; T3 , 37 % ; T4 , 0 % ) . Only 18 % of the initially enrolled population is alive with a preserved bladder . The 
    Output:
    