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: Between January 1991 and October 1993 , 32 consecutive patients with documented primary bladder tumours invading muscle received 3 cycles of methotrexate , vinblastin , doxorubicin and cisplatin ( MVAC ) . The disease was re-staged by bimanual examination with the patient under anaesthesia , CT scanning and transurethral biopsy or resection . Of the 32 patients 2 underwent total or partial cystectomy and 30 did not , because re-staging showed no residual tumour in 8 ( 25 % ) , stage T1–2 in 12 ( 37.5 % ) and far-advanced tumour in 10 ( 31.2 % ) . The median follow-up was 2.8 years . Twelve patients with stage T1–2 tumour have required TUR , and cystectomy has not been necessary . Two patients who underwent total/partial cystectomy were all downstaged pathologically . Of the 10 failures 5 patients died of disease and 5 are alive with metastatic disease . The overall survival rate was 84.3 % ( 27 of 32 ) and was 96.8 % for patients with a functioning bladder . The data suggested that this active regimen can clinical ly induce down-staging in a significant number of patients with primary muscle-infiltrating bladder tumours .  Transurethral resection plus MVAC chemotherapy is important for increased curability in patients with advanced bladder cancer PURPOSE We conducted a phase II trial of neoadjuvant paclitaxel , carboplatin and gemcitabine as well as transurethral resection of bladder tumor to evaluate the clinical T0 ( cT0 ) rate with paclitaxel , carboplatin and gemcitabine , and to study cystoscopic surveillance or immediate cystectomy for patients with cT0 status following chemotherapy .  MATERIAL S AND METHODS Patients with T2-T4a chemotherapy and radiation naive urothelial cancer were eligible . T2 + tumor had to be diagnosed by transurethral bladder tumor resection followed by a second transurethral bladder tumor resection to confirm persistent disease within 16 weeks of the first resection . Three cycles of paclitaxel , carboplatin and gemcitabine were administered within 8 weeks of the second transurethral bladder tumor resection . Patients with cT0 status after paclitaxel , carboplatin and gemcitabine therapy could elect immediate cystectomy or cystoscopic surveillance , and those with greater than cT0 status were to undergo immediate cystectomy . RESULTS Of 77 patients 74 were assessable , and cT0 status after paclitaxel , carboplatin and gemcitabine was achieved in 34 of 74 patients ( 46 % ) . Of the 34 patients with cT0 status 10 underwent immediate cystectomy , 6 of whom had persistent cancer . Persistent tumor at transurethral bladder tumor resection was seen in 28 patients ( 38 % ) and 21 underwent cystectomy . Thus , 35 of 74 patients underwent cystectomy . With a median followup of 22 months 2-year overall survival was 59 % ( 95 % CI 45 , 72 ) and among cT0 cases it was 75 % ( 95 % CI 57 , 93 ) . CONCLUSIONS Although neoadjuvant paclitaxel , carboplatin and gemcitabine had a promising 46 % cT0 rate , the study failed to meet the primary objective as there was an unacceptably high rate ( 60 % ) of persistent cancer at cystectomy in patients presumed to have pT0 status . Patients completing neoadjuvant chemotherapy should strongly consider definitive local therapy rather than cystoscopic surveillance regardless of post-chemotherapy cT0 status PURPOSE To assess the safety , tolerance , and efficacy of transurethral surgery plus concomitant cisplatin , 5-fluorouracil ( 5-FU ) , and radiation therapy in conjunction with selective bladder preservation in patients with muscle-invading bladder cancer . Patients and Methods . Thirty-four eligible patients with clinical stage T2-T4a , Nx M0 bladder cancer without hydronephrosis were entered into a protocol aim ed at selective bladder preservation . Treatment began with as complete a transurethral resection as possible followed by induction chemoradiation . This consisted of cisplatin 15 mg/m(2 ) i.v . and 5-fluorouracil ( 5-FU ) 400 mg/m(2 ) i.v . in the mornings on d 1 , 2 , 3 , 15 , 16 , and 17 . On d 1 , 3 , 15 , and 17 , radiation was given immediately following the chemotherapy using twice-a-day 3 Gy per fraction cores to the pelvis for a total radiation dose of 24 Gy . Response was evaluated by cystoscopy , cytology , and rebiopsy four weeks later . Patients with a complete response received consolidation therapy with the same drugs and doses on d 1 , 2 , 3 , 15 , 16 , and 17 combined with twice-daily radiation therapy to the bladder and bladder tumor volume of 2.5 Gy per fraction for a total consolidation dose of 20 Gy and a total induction plus consolidation dose to the bladder and bladder tumor of 44 Gy . Patients who did not achieve a complete response were advised to undergo prompt cystectomy , as were those with a subsequent invasive recurrence . The median follow up is 29 months . RESULTS Of the 34 eligible patients , 26 had a visibly complete transurethral resection . One patient did not complete induction treatment due to acute hematologic toxicity . After induction treatment , 22 ( 67 % ) of the 33 patients had no tumor detectable on urine cytology or rebiopsy . Of the 11 patients who still had detectable tumor , six underwent radical cystectomy and five underwent consolidation chemoradiation ( one because of refusal to have the recommended cystectomy and four because the treating institutions erroneously assigned them to receive consolidation chemoradiation rather than cystectomy ) . No patient has required a cystectomy for radiation toxicity . Six patients have died of bladder cancer . The actuarial overall survival at three years is 83 % . The probability of surviving with an intact bladder is 66 % at three years . A total of seven patients ( 21 % ) developed grade 3 or grade 4 hematologic toxicity in conjunction with this treatment . CONCLUSION This aggressive protocol comprising local surgery plus concurrent 5-FU , cisplatin , and high-dose hypofractionated radiation has been associated with moderately severe hematologic toxicity . Longer follow-up will be necessary to assess efficacy . Both the 67 % complete response rate to induction therapy and the 66 % three-year survival with an intact bladder are encouraging Neoadjuvant chemotherapy for patients with muscle‐invasive bladder carcinoma is given to treat micrometastases and to preserve the bladder . The objective of this study was to evaluate the possibility of bladder preservation in patients with muscle‐invasive bladder carcinoma who were treated with neoadjuvant methotrexate , vinblastine , doxorubicin , and cisplatin ( M‐VAC ) chemotherapy PURPOSE We proved the feasibility of radical transurethral bladder tumor resection in selected patients with muscle invasive bladder cancer with a minimum followup of more than 15 years and investigated the impact of patient age on survival . A followup schedule was developed based on progression and recurrence during this period . MATERIAL S AND METHODS A phase II nonr and omized trial was design ed including patients with muscle invasive bladder cancer with negative biopsies of tumor bed who were apparently healthy after undergoing complete transurethral bladder tumor resection . Patients with positive biopsies , or with macroscopically residual tumor , hydronephrosis or metastasis were excluded from study . In this trial 133 patients fulfilled the inclusion criteria and had a minimum followup of more than 15 years .  RESULTS Cancer specific survival was 81.9 % , 79.5 % and 76.7 % , and progression-free survival with bladder preservation was 75.5 % , 64.9 % and 57.8 % at 5 , 10 and 15 years , respectively . Patient age had a negative impact on overall survival on univariate ( HR 0.842 , p = 0.049 ) and multivariate analyses ( HR 1.062 , p = 0.000 ) , and according to median and quartile age stratifications ( p = 0.000 and p = 0.000 , respectively ) . However , age did not have a negative impact on cancer specific survival even when following the same stratifications . Although progression and recurrence were concentrated during the first 3 years ( 70 % and 65 % , respectively ) , both steadily increased afterward . A followup schedule was developed according to this sequence of events . CONCLUSIONS Radical transurethral bladder tumor resection is a reliable therapeutic approach for patients with muscle invasive bladder cancer after complete tumor resection and with negative biopsies of the tumor bed . These results are consistent in all age ranges To examine combination cisplatin and twice-daily accelerated irradiation ( RT ) after aggressive transurethral resection of bladder tumor ( TURBT ) in an attempt to preserve the bladder and to determine the likelihood that patients who complete this regimen could then complete three cycles of methotrexate , cisplatin , vinblastine ( MCV ) chemotherapy .  Between 1998 and 2000 , 52 patients with Stage T2-T4aN0M0 disease , from 17 institutions , were entered into the trial . Forty-seven patients were deemed eligible ; the planned accrual was 40 . Of the 46 patients , 68 % were > 60 years old , 70 % were men , and 96 % had a Karnofsky score > /=90 . The clinical T stage was T2 in 66 % , T3a in 25 % , and T3b in 9 % . The median follow-up at the time of analysis was 26 months . The protocol required TURBT within 6 weeks of the initiation of induction therapy . Induction treatment involved 13 days of concomitant boost RT , 1.8 Gy to the pelvis in the morning followed by 1.6 Gy to the tumor 4 - 6 h later . For sensitization , cisplatin ( 20 mg/m(2 ) ) was given on the first 3 days of each treatment week . Three to four weeks after induction , patients were evaluated cystoscopically for residual disease . Patients whose biopsies and cytologic evaluations showed no disease completed consolidation chemoirradiation . Patients with residual tumor went on to cystectomy . After either consolidation or cystectomy , patients were to complete three cycles of MCV chemotherapy . Of the 47 patients , 45 % completed all phases of the protocol treatment with minor , or no , deviations . Five patients refused either the postinduction evaluation or cystectomy and 6 refused adjuvant chemotherapy . The CR rate after induction therapy was 74 % . For 2 patients , residual disease after induction was limited to positive cytologic findings , and for 8 patients , biopsy of the primary site revealed persistence . Of the 8 cystectomy patients , 2 had no evidence of disease in the bladder at pathologic review of the surgery specimen . Grade 3 toxicity related to chemotherapy was observed in 11 % of patients during both induction and consolidation , and in 41 % during adjuvant chemotherapy . A total of 8 patients ( 36 % of those receiving adjuvant chemotherapy ) went on to develop Grade 4 neutropenia or thrombocytopenia during additional adjuvant chemotherapy .  Grade 3 toxicity due to RT was seen in 4 % and 0 % of patients during induction and consolidation , respectively . One patient developed Grade 4 hydronephrosis during consolidation . The projected 36-month value for locoregional failure , distant metastasis , overall survival , and bladder-intact survival was 27 % , 29 % , 61 % , and 48 % , respectively . After aggressive TURBT , twice-daily accelerated RT initiated in concomitant-boost format is well tolerated and results in a rate of complete response ( 74 % ) similar to that in previous bladder-sparing trials . The projected 2-year values for locoregional control , bladder-intact survival , and overall survival were also consistent with previously reported trials of bladder-sparing treatment . With only 45 % of patients completing three cycles of MCV , this form of adjuvant chemotherapy appears to be poorly tolerated by most patients PURPOSE To assess the effectiveness of two approaches of organ-sparing treatment in patients with invasive transitional cell bladder carcinoma . PATIENTS AND METHODS During the period from June 1996 to June 2000 , 33 patients with invasive transitional cell carcinoma ( T2 - 4 ) of the bladder were treated . Patients were divided into two groups . Group A included 17 patients treated with CMV systemic chemotherapy ( methotrexate 30 mg/m(2 ) and vinblast 
    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: Between January 1991 and October 1993 , 32 consecutive patients with documented primary bladder tumours invading muscle received 3 cycles of methotrexate , vinblastin , doxorubicin and cisplatin ( MVAC ) . The disease was re-staged by bimanual examination with the patient under anaesthesia , CT scanning and transurethral biopsy or resection . Of the 32 patients 2 underwent total or partial cystectomy and 30 did not , because re-staging showed no residual tumour in 8 ( 25 % ) , stage T1–2 in 12 ( 37.5 % ) and far-advanced tumour in 10 ( 31.2 % ) . The median follow-up was 2.8 years . Twelve patients with stage T1–2 tumour have required TUR , and cystectomy has not been necessary . Two patients who underwent total/partial cystectomy were all downstaged pathologically . Of the 10 failures 5 patients died of disease and 5 are alive with metastatic disease . The overall survival rate was 84.3 % ( 27 of 32 ) and was 96.8 % for patients with a functioning bladder . The data suggested that this active regimen can clinical ly induce down-staging in a significant number of patients with primary muscle-infiltrating bladder tumours .  Transurethral resection plus MVAC chemotherapy is important for increased curability in patients with advanced bladder cancer PURPOSE We conducted a phase II trial of neoadjuvant paclitaxel , carboplatin and gemcitabine as well as transurethral resection of bladder tumor to evaluate the clinical T0 ( cT0 ) rate with paclitaxel , carboplatin and gemcitabine , and to study cystoscopic surveillance or immediate cystectomy for patients with cT0 status following chemotherapy .  MATERIAL S AND METHODS Patients with T2-T4a chemotherapy and radiation naive urothelial cancer were eligible . T2 + tumor had to be diagnosed by transurethral bladder tumor resection followed by a second transurethral bladder tumor resection to confirm persistent disease within 16 weeks of the first resection . Three cycles of paclitaxel , carboplatin and gemcitabine were administered within 8 weeks of the second transurethral bladder tumor resection . Patients with cT0 status after paclitaxel , carboplatin and gemcitabine therapy could elect immediate cystectomy or cystoscopic surveillance , and those with greater than cT0 status were to undergo immediate cystectomy . RESULTS Of 77 patients 74 were assessable , and cT0 status after paclitaxel , carboplatin and gemcitabine was achieved in 34 of 74 patients ( 46 % ) . Of the 34 patients with cT0 status 10 underwent immediate cystectomy , 6 of whom had persistent cancer . Persistent tumor at transurethral bladder tumor resection was seen in 28 patients ( 38 % ) and 21 underwent cystectomy . Thus , 35 of 74 patients underwent cystectomy . With a median followup of 22 months 2-year overall survival was 59 % ( 95 % CI 45 , 72 ) and among cT0 cases it was 75 % ( 95 % CI 57 , 93 ) . CONCLUSIONS Although neoadjuvant paclitaxel , carboplatin and gemcitabine had a promising 46 % cT0 rate , the study failed to meet the primary objective as there was an unacceptably high rate ( 60 % ) of persistent cancer at cystectomy in patients presumed to have pT0 status . Patients completing neoadjuvant chemotherapy should strongly consider definitive local therapy rather than cystoscopic surveillance regardless of post-chemotherapy cT0 status PURPOSE To assess the safety , tolerance , and efficacy of transurethral surgery plus concomitant cisplatin , 5-fluorouracil ( 5-FU ) , and radiation therapy in conjunction with selective bladder preservation in patients with muscle-invading bladder cancer . Patients and Methods . Thirty-four eligible patients with clinical stage T2-T4a , Nx M0 bladder cancer without hydronephrosis were entered into a protocol aim ed at selective bladder preservation . Treatment began with as complete a transurethral resection as possible followed by induction chemoradiation . This consisted of cisplatin 15 mg/m(2 ) i.v . and 5-fluorouracil ( 5-FU ) 400 mg/m(2 ) i.v . in the mornings on d 1 , 2 , 3 , 15 , 16 , and 17 . On d 1 , 3 , 15 , and 17 , radiation was given immediately following the chemotherapy using twice-a-day 3 Gy per fraction cores to the pelvis for a total radiation dose of 24 Gy . Response was evaluated by cystoscopy , cytology , and rebiopsy four weeks later . Patients with a complete response received consolidation therapy with the same drugs and doses on d 1 , 2 , 3 , 15 , 16 , and 17 combined with twice-daily radiation therapy to the bladder and bladder tumor volume of 2.5 Gy per fraction for a total consolidation dose of 20 Gy and a total induction plus consolidation dose to the bladder and bladder tumor of 44 Gy . Patients who did not achieve a complete response were advised to undergo prompt cystectomy , as were those with a subsequent invasive recurrence . The median follow up is 29 months . RESULTS Of the 34 eligible patients , 26 had a visibly complete transurethral resection . One patient did not complete induction treatment due to acute hematologic toxicity . After induction treatment , 22 ( 67 % ) of the 33 patients had no tumor detectable on urine cytology or rebiopsy . Of the 11 patients who still had detectable tumor , six underwent radical cystectomy and five underwent consolidation chemoradiation ( one because of refusal to have the recommended cystectomy and four because the treating institutions erroneously assigned them to receive consolidation chemoradiation rather than cystectomy ) . No patient has required a cystectomy for radiation toxicity . Six patients have died of bladder cancer . The actuarial overall survival at three years is 83 % . The probability of surviving with an intact bladder is 66 % at three years . A total of seven patients ( 21 % ) developed grade 3 or grade 4 hematologic toxicity in conjunction with this treatment . CONCLUSION This aggressive protocol comprising local surgery plus concurrent 5-FU , cisplatin , and high-dose hypofractionated radiation has been associated with moderately severe hematologic toxicity . Longer follow-up will be necessary to assess efficacy . Both the 67 % complete response rate to induction therapy and the 66 % three-year survival with an intact bladder are encouraging Neoadjuvant chemotherapy for patients with muscle‐invasive bladder carcinoma is given to treat micrometastases and to preserve the bladder . The objective of this study was to evaluate the possibility of bladder preservation in patients with muscle‐invasive bladder carcinoma who were treated with neoadjuvant methotrexate , vinblastine , doxorubicin , and cisplatin ( M‐VAC ) chemotherapy PURPOSE We proved the feasibility of radical transurethral bladder tumor resection in selected patients with muscle invasive bladder cancer with a minimum followup of more than 15 years and investigated the impact of patient age on survival . A followup schedule was developed based on progression and recurrence during this period . MATERIAL S AND METHODS A phase II nonr and omized trial was design ed including patients with muscle invasive bladder cancer with negative biopsies of tumor bed who were apparently healthy after undergoing complete transurethral bladder tumor resection . Patients with positive biopsies , or with macroscopically residual tumor , hydronephrosis or metastasis were excluded from study . In this trial 133 patients fulfilled the inclusion criteria and had a minimum followup of more than 15 years .  RESULTS Cancer specific survival was 81.9 % , 79.5 % and 76.7 % , and progression-free survival with bladder preservation was 75.5 % , 64.9 % and 57.8 % at 5 , 10 and 15 years , respectively . Patient age had a negative impact on overall survival on univariate ( HR 0.842 , p = 0.049 ) and multivariate analyses ( HR 1.062 , p = 0.000 ) , and according to median and quartile age stratifications ( p = 0.000 and p = 0.000 , respectively ) . However , age did not have a negative impact on cancer specific survival even when following the same stratifications . Although progression and recurrence were concentrated during the first 3 years ( 70 % and 65 % , respectively ) , both steadily increased afterward . A followup schedule was developed according to this sequence of events . CONCLUSIONS Radical transurethral bladder tumor resection is a reliable therapeutic approach for patients with muscle invasive bladder cancer after complete tumor resection and with negative biopsies of the tumor bed . These results are consistent in all age ranges To examine combination cisplatin and twice-daily accelerated irradiation ( RT ) after aggressive transurethral resection of bladder tumor ( TURBT ) in an attempt to preserve the bladder and to determine the likelihood that patients who complete this regimen could then complete three cycles of methotrexate , cisplatin , vinblastine ( MCV ) chemotherapy .  Between 1998 and 2000 , 52 patients with Stage T2-T4aN0M0 disease , from 17 institutions , were entered into the trial . Forty-seven patients were deemed eligible ; the planned accrual was 40 . Of the 46 patients , 68 % were > 60 years old , 70 % were men , and 96 % had a Karnofsky score > /=90 . The clinical T stage was T2 in 66 % , T3a in 25 % , and T3b in 9 % . The median follow-up at the time of analysis was 26 months . The protocol required TURBT within 6 weeks of the initiation of induction therapy . Induction treatment involved 13 days of concomitant boost RT , 1.8 Gy to the pelvis in the morning followed by 1.6 Gy to the tumor 4 - 6 h later . For sensitization , cisplatin ( 20 mg/m(2 ) ) was given on the first 3 days of each treatment week . Three to four weeks after induction , patients were evaluated cystoscopically for residual disease . Patients whose biopsies and cytologic evaluations showed no disease completed consolidation chemoirradiation . Patients with residual tumor went on to cystectomy . After either consolidation or cystectomy , patients were to complete three cycles of MCV chemotherapy . Of the 47 patients , 45 % completed all phases of the protocol treatment with minor , or no , deviations . Five patients refused either the postinduction evaluation or cystectomy and 6 refused adjuvant chemotherapy . The CR rate after induction therapy was 74 % . For 2 patients , residual disease after induction was limited to positive cytologic findings , and for 8 patients , biopsy of the primary site revealed persistence . Of the 8 cystectomy patients , 2 had no evidence of disease in the bladder at pathologic review of the surgery specimen . Grade 3 toxicity related to chemotherapy was observed in 11 % of patients during both induction and consolidation , and in 41 % during adjuvant chemotherapy . A total of 8 patients ( 36 % of those receiving adjuvant chemotherapy ) went on to develop Grade 4 neutropenia or thrombocytopenia during additional adjuvant chemotherapy .  Grade 3 toxicity due to RT was seen in 4 % and 0 % of patients during induction and consolidation , respectively . One patient developed Grade 4 hydronephrosis during consolidation . The projected 36-month value for locoregional failure , distant metastasis , overall survival , and bladder-intact survival was 27 % , 29 % , 61 % , and 48 % , respectively . After aggressive TURBT , twice-daily accelerated RT initiated in concomitant-boost format is well tolerated and results in a rate of complete response ( 74 % ) similar to that in previous bladder-sparing trials . The projected 2-year values for locoregional control , bladder-intact survival , and overall survival were also consistent with previously reported trials of bladder-sparing treatment . With only 45 % of patients completing three cycles of MCV , this form of adjuvant chemotherapy appears to be poorly tolerated by most patients PURPOSE To assess the effectiveness of two approaches of organ-sparing treatment in patients with invasive transitional cell bladder carcinoma . PATIENTS AND METHODS During the period from June 1996 to June 2000 , 33 patients with invasive transitional cell carcinoma ( T2 - 4 ) of the bladder were treated . Patients were divided into two groups . Group A included 17 patients treated with CMV systemic chemotherapy ( methotrexate 30 mg/m(2 ) and vinblast 
    Output:
    