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 High-dose chemotherapy ( HD-CT ) is able to circumvent platinum resistance of resistant/refractory germ-cell tumors ( GCTs ) , but expectancy of cure remains low . New strategies are needed with new drugs and a sequential approach . MATERIAL S AND METHODS Patients with relapsed poor-prognosis GCTs were scheduled to receive two cycles combining epirubicin and paclitaxel ( Taxol ) followed by three consecutive HD-CT supported by stem cell transplantation [ one course combining cyclophosphamide , 3 g/m(2 ) + thiotepa , 400 mg/m(2 ) , followed by two ICE regimens ( ifosfamide , 10 g/m(2 ) , carboplatin , AUC 20 , etoposide , 1500 mg/m(2 ) ) ] . RESULTS From March 1998 to September 2001 ( median follow-up , 31.8 months ) , 45 patients ( median age , 28 years ) were enrolled in this phase II study . Twenty-two patients received the complete course . Twenty-five patients died from progression and five from toxicity . The overall response rate was 37.7 % , including an 8.9 % complete response rate . The median overall survival was 11.8 months . The 3-year survival and progression-free survival rate was 23.5 % . The ' Beyer ' prognostic score predicted the outcome after HD-CT . CONCLUSION Although our results warrant further studies on HD-CT in relapsed poor prognosis GCTs , patients with a Beyer score > 2 did not benefit from this approach and should not be enrolled in HD-CT trials . Better selection criteria have to be fulfilled in forthcoming studies BACKGROUND High-dose chemotherapy ( HDCT ) is an effective salvage treatment of germ-cell tumors ( GCTs ) patients . In the first salvage setting , 30%-70 % of patients may achieve durable remissions . Even when HDCT is administered as subsequent salvage treatment , up to 20 % of patients may still be definitively cured . However , patients with refractory/relapsed disease still have a very poor long-term prognosis , requiring earlier intervention of HDCT . PATIENTS AND METHODS This phase II trial was addressed to nonrefractory patients failing Cisplatin-based chemotherapy . Inclusion criteria included seminomatous GCT in relapse after two lines of chemotherapy , nonseminomatous GCT in relapse after first or second lines , partial remission after first line , primary mediastinal GCT in first relapse . Patients received two cycles combining Epirubicin and Paclitaxel ( Epi-Tax ) , followed by three consecutive HDCT , one using a Paclitaxel/Thiotepa ( Thio-Tax ) association and two using the 5-day Ifosfamide-Carboplatin-Etoposide regimen . The main objective was to determine the complete response rate . RESULTS Forty-five patients were included between September 2004 and December 2007 : 44 received the first HDCT cycle , 39 two HDCT cycles , 29 could receive the whole protocol . Sixteen patients did not receive the entire protocol , including eight ( 17.7 % ) for toxic side-effects . Two patients ( 4.4 % ) died of toxicities , and 17 ( 37.7 % ) of disease progression . With a median follow-up time of 26 months ( range , 4 - 51 ) , the final overall response rate was 48.8 % ( including a complete response rate of 15.5 % and a partial response/negative serum markers rate of 26.6 % ) in an intent-to-treat analysis . The median progression-free survival ( PFS ) and overall survival ( OS ) times were 22 months [ 95 % confidence interval ( CI ) 2-not reached ] and 32 months ( 95 % CI 4 - 49 ) , respectively . The 2-year PFS was a plateau setup at 50 % ( 95 % CI 32 - 67 ) and the 2-year OS was 66 % ( 95 % CI 44 - 81 ) . CONCLUSION The TAXIF II protocol was effective in nonrefractory GCT patients failing Cisplatin-based chemotherapy . The toxic death rate remained acceptable in the field of HDCT regimens . TRIAL REGISTRATION NUMBER NCT00231582 STUDY OBJECTIVE To determine the efficacy of the addition of ifosfamide to cisplatin plus etoposide ( VIP ) , or vinblastine ( VeIP ) , in patients with recurrent germ cell tumors . DESIGN Nonr and omized , prospect i ve phase II trial . SETTING Tertiary referral university hospital . PATIENTS Fifty-six of fifty-eight entered patients with measurable and progressive recurrent germ cell tumors of testicular ( 46 patients ) , ovarian ( 1 patient ) , and extragonadal ( 9 patients ) origin were evaluable for response after not being cured with cisplatin , vinblastine , and etoposide regimens . INTERVENTIONS Patients were administered cisplatin ( 20 mg/m2 body surface area daily for 5 days ) , ifosfamide ( 1.2 g daily for 5 days ) , plus either etoposide ( 75 mg daily for 5 days ) or vinblastine ( 0.11 mg/kg body weight on days 1 and 2 ) . In addition , vigorous intravenous hydration therapy with normal saline ( 100 to 125 mL/h ) was administered during the treatment course . Uroepithelial protective agents , N-acetylcysteine ( orally ) or mesna ( intravenously ) , were administered . Four courses were administered to responding patients every 3 weeks . When complete excision was feasible , surgical resection of residual tumor was done approximately 6 to 8 weeks after chemotherapy . MEASUREMENTS AND MAIN RESULTS Twelve of fifty-six evaluable patients had a complete remission with chemotherapy alone , whereas 8 additional patients were free of disease after resection of teratoma ( 3 patients ) or carcinoma ( 5 patients ) for a total disease-free rate of 36 % ( 95 % CI , 23.4 to 49.6 ) . The 95 % CI median duration of remission for these patients is 34 months ( range , 3 to more than 42 ; 95 % CI , 9 months to infinity ) , and the median survival for all eligible patients is 12.7 months ( 95 % CI , 10 months to 26 months ) , with 15 of the 20 patients who achieved disease-free status alive 18 to 53 months or more . Nine of fifty-eight patients remain free of disease , including 7 patients for 2 years or longer . Hematologic and nephrotoxicity were the predominant drug-related toxicities , with one drug-related death secondary to pneumonia . CONCLUSIONS Ifosfamide combination chemotherapy as third-line or greater therapy can produce durable complete remissions in heavily pretreated patients with recurrent germ cell tumors High-dose regimes containing etoposide , carboplatin and an oxazaphospharine can salvage 30–40 % of patients with relapsed or refractory male germ cell tumours ( GCTs ) . The additional benefit of paclitaxel in such high-dose therapy has not been tested . Between March 1995 and November 2002 , 36 male GCT patients were treated with Carbop-EC-T ( paclitaxel 75 mg m−2 , etoposide 450 mg m−2 , carboplatin AUC 10 on days −7 , −5 and −3 and cyclophosphamide 60 mg kg−1 on days −5 and −3 ) followed by peripheral blood stem cell infusion ( day 0 ) . The 1-year overall survival rate for all patients is 67 % ( median follow-up 29 months ) . For the 24 patients with cisplatin-sensitive disease , the 1-year overall and event-free survivals are 88 and 64 % , respectively . For those with cisplatin refractory or absolutely refractory disease , the 1-year overall survival is 25 % . In all , 12 patients relapsed at a median duration of 5 months , 11 of whom have died . There were also six treatment-related deaths , five associated with pneumonitis . Pulmonary toxicity has been reported with paclitaxel in other high-dose regimes . Since altering our protocol so that paclitaxel is infused over 24 h with steroid prophylaxis , only one of 18 patients ( 13 testicular GCTs and five other tumour types ) has had a treatment-related death . Our results suggest that Carbop-EC-T may enable a greater proportion of patients with relapsed and refractory GCTs to enter long-term remission We evaluated high-dose carboplatin and etoposide with autologous bone marrow stem cell support in the salvage treatment of patients with metastatic germ cell tumours who had failed previous chemotherapy . The treatment programme comprised initial conventional dose chemotherapy .  23 patients received a first cycle of high-dose treatment , and 12 who showed no evidence of progression had a second cycle 2 - 3 months later . 8 of the 23 patients treated with high-dose chemotherapy are alive in remission 4 - 29 months from the start of high-dose treatment . 3 of these 8 required further treatment for recurrence . In the initial part of the study , the dose of carboplatin was escalated in successive patients . Grade 3/4 treatment-related toxicity occurred in 4 of 18 patients ( 1 fatal ) who received carboplatin doses to give a AUC ( area under the serum concentration/time curve ) of 30 mg.min/ml or less and 3 of 5 patients ( 2 fatal ) who received higher doses . We , therefore , recommend 30 mg.min/ml for further evaluation in chemotherapy sensitive patients PURPOSE To study feasibility and efficacy of a new salvage regimen in patients with relapsed and /or refractory germ cell tumors . PATIENTS AND METHODS Between May 1995 and February 1997 , 80 patients were entered onto a phase II study . Conventional-dose salvage treatment with three cycles of paclitaxel 175 mg/m(2 ) , ifosfamide 5 x 1.2 g/m(2 ) , and cisplatin 5 x 20 mg/m(2 ) ( TIP ) was followed by one cycle of high-dose chemotherapy ( HDCT ) with carboplatin 500 mg/m(2 ) x 3 , etoposide 600 mg/m(2 ) x 4 , and thiotepa 150 to 250 mg/m(2 ) x 3 ( CET ) . In 23 patients , one additional cycle of paclitaxel 175 mg/m(2 ) and ifosfamide 5 g/m(2 ) ( TI ) was given immediately before TIP to improve stem-cell mobilization . RESULTS Fifty-five ( 69 % ) of 80 patients responded to TIP , 24 ( 30 % ) of 80 patients had stable disease ( n = 5 ) or tumor progression ( n = 19 ) , and one patient died . Only 62 ( 78 % ) of 80 patients received subsequent HDCT . Among those , 41 ( 66 % ) of 62 patients responded and 20 ( 32 % ) of 62 patients had stable disease ( n = 3 ) or tumor progression ( n = 17 ) . One patient died after HDCT from multiorgan failure . Survival probabilities at 3 years were 30 % for overall and 25 % for event-free survival . Peripheral neurotoxicity with sensorimotor impairment grade 2 through 4 in 29 % , paresthesias grade 2 through 4 in 24 % , and skin toxicity grade 2 through 3 in 15 % of patients were the most relevant side effects . CONCLUSION Treatment with TIP followed by high-dose CET is feasible and can induce long-term remissions in 25 % of patients with relapsed or refractory germ cell tumors . Peripheral nervous toxicity in approximately one third of patients is a disadvantage of this salvage strategy BACKGROUND Incomplete remission or relapse from first-line chemotherapy has poor prognosis in male germ cell tumour patients . This phase III r and omised trial compares conventional salvage to high-dose-intensification chemotherapy . PATIENTS AND METHODS Between February 1994 and September 2001 , 280 patients from 43 institutions in 11 countries , were r and omly assigned to receive either four cycles of cisplatin , ifosfamide and etoposide ( or vinblastine ) ( arm A ) , or three such cycles followed by high-dose carboplatin , etoposide and cyclophosphamide ( CarboPEC ) with haematopoietic stem cell support ( arm B ) . RESULTS Similar complete and partial response rates were observed in both treatment arms ( 56 % ; 95 % CI 50 % to 62 % ) . There were 3 % and 7 % toxic deaths in arms A and B , respectively . No significant improvements with CarboPEC were observed in either 3-year event-free survival ( 35 % versus 42 % , P=0.16 ) or overall survival ( 53 % ; 95 % CI 46 % to 59 % ) . Complete responders with CarboPEC had a significant improvement in disease-free survival ( 55 % versus  
    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 High-dose chemotherapy ( HD-CT ) is able to circumvent platinum resistance of resistant/refractory germ-cell tumors ( GCTs ) , but expectancy of cure remains low . New strategies are needed with new drugs and a sequential approach . MATERIAL S AND METHODS Patients with relapsed poor-prognosis GCTs were scheduled to receive two cycles combining epirubicin and paclitaxel ( Taxol ) followed by three consecutive HD-CT supported by stem cell transplantation [ one course combining cyclophosphamide , 3 g/m(2 ) + thiotepa , 400 mg/m(2 ) , followed by two ICE regimens ( ifosfamide , 10 g/m(2 ) , carboplatin , AUC 20 , etoposide , 1500 mg/m(2 ) ) ] . RESULTS From March 1998 to September 2001 ( median follow-up , 31.8 months ) , 45 patients ( median age , 28 years ) were enrolled in this phase II study . Twenty-two patients received the complete course . Twenty-five patients died from progression and five from toxicity . The overall response rate was 37.7 % , including an 8.9 % complete response rate . The median overall survival was 11.8 months . The 3-year survival and progression-free survival rate was 23.5 % . The ' Beyer ' prognostic score predicted the outcome after HD-CT . CONCLUSION Although our results warrant further studies on HD-CT in relapsed poor prognosis GCTs , patients with a Beyer score > 2 did not benefit from this approach and should not be enrolled in HD-CT trials . Better selection criteria have to be fulfilled in forthcoming studies BACKGROUND High-dose chemotherapy ( HDCT ) is an effective salvage treatment of germ-cell tumors ( GCTs ) patients . In the first salvage setting , 30%-70 % of patients may achieve durable remissions . Even when HDCT is administered as subsequent salvage treatment , up to 20 % of patients may still be definitively cured . However , patients with refractory/relapsed disease still have a very poor long-term prognosis , requiring earlier intervention of HDCT . PATIENTS AND METHODS This phase II trial was addressed to nonrefractory patients failing Cisplatin-based chemotherapy . Inclusion criteria included seminomatous GCT in relapse after two lines of chemotherapy , nonseminomatous GCT in relapse after first or second lines , partial remission after first line , primary mediastinal GCT in first relapse . Patients received two cycles combining Epirubicin and Paclitaxel ( Epi-Tax ) , followed by three consecutive HDCT , one using a Paclitaxel/Thiotepa ( Thio-Tax ) association and two using the 5-day Ifosfamide-Carboplatin-Etoposide regimen . The main objective was to determine the complete response rate . RESULTS Forty-five patients were included between September 2004 and December 2007 : 44 received the first HDCT cycle , 39 two HDCT cycles , 29 could receive the whole protocol . Sixteen patients did not receive the entire protocol , including eight ( 17.7 % ) for toxic side-effects . Two patients ( 4.4 % ) died of toxicities , and 17 ( 37.7 % ) of disease progression . With a median follow-up time of 26 months ( range , 4 - 51 ) , the final overall response rate was 48.8 % ( including a complete response rate of 15.5 % and a partial response/negative serum markers rate of 26.6 % ) in an intent-to-treat analysis . The median progression-free survival ( PFS ) and overall survival ( OS ) times were 22 months [ 95 % confidence interval ( CI ) 2-not reached ] and 32 months ( 95 % CI 4 - 49 ) , respectively . The 2-year PFS was a plateau setup at 50 % ( 95 % CI 32 - 67 ) and the 2-year OS was 66 % ( 95 % CI 44 - 81 ) . CONCLUSION The TAXIF II protocol was effective in nonrefractory GCT patients failing Cisplatin-based chemotherapy . The toxic death rate remained acceptable in the field of HDCT regimens . TRIAL REGISTRATION NUMBER NCT00231582 STUDY OBJECTIVE To determine the efficacy of the addition of ifosfamide to cisplatin plus etoposide ( VIP ) , or vinblastine ( VeIP ) , in patients with recurrent germ cell tumors . DESIGN Nonr and omized , prospect i ve phase II trial . SETTING Tertiary referral university hospital . PATIENTS Fifty-six of fifty-eight entered patients with measurable and progressive recurrent germ cell tumors of testicular ( 46 patients ) , ovarian ( 1 patient ) , and extragonadal ( 9 patients ) origin were evaluable for response after not being cured with cisplatin , vinblastine , and etoposide regimens . INTERVENTIONS Patients were administered cisplatin ( 20 mg/m2 body surface area daily for 5 days ) , ifosfamide ( 1.2 g daily for 5 days ) , plus either etoposide ( 75 mg daily for 5 days ) or vinblastine ( 0.11 mg/kg body weight on days 1 and 2 ) . In addition , vigorous intravenous hydration therapy with normal saline ( 100 to 125 mL/h ) was administered during the treatment course . Uroepithelial protective agents , N-acetylcysteine ( orally ) or mesna ( intravenously ) , were administered . Four courses were administered to responding patients every 3 weeks . When complete excision was feasible , surgical resection of residual tumor was done approximately 6 to 8 weeks after chemotherapy . MEASUREMENTS AND MAIN RESULTS Twelve of fifty-six evaluable patients had a complete remission with chemotherapy alone , whereas 8 additional patients were free of disease after resection of teratoma ( 3 patients ) or carcinoma ( 5 patients ) for a total disease-free rate of 36 % ( 95 % CI , 23.4 to 49.6 ) . The 95 % CI median duration of remission for these patients is 34 months ( range , 3 to more than 42 ; 95 % CI , 9 months to infinity ) , and the median survival for all eligible patients is 12.7 months ( 95 % CI , 10 months to 26 months ) , with 15 of the 20 patients who achieved disease-free status alive 18 to 53 months or more . Nine of fifty-eight patients remain free of disease , including 7 patients for 2 years or longer . Hematologic and nephrotoxicity were the predominant drug-related toxicities , with one drug-related death secondary to pneumonia . CONCLUSIONS Ifosfamide combination chemotherapy as third-line or greater therapy can produce durable complete remissions in heavily pretreated patients with recurrent germ cell tumors High-dose regimes containing etoposide , carboplatin and an oxazaphospharine can salvage 30–40 % of patients with relapsed or refractory male germ cell tumours ( GCTs ) . The additional benefit of paclitaxel in such high-dose therapy has not been tested . Between March 1995 and November 2002 , 36 male GCT patients were treated with Carbop-EC-T ( paclitaxel 75 mg m−2 , etoposide 450 mg m−2 , carboplatin AUC 10 on days −7 , −5 and −3 and cyclophosphamide 60 mg kg−1 on days −5 and −3 ) followed by peripheral blood stem cell infusion ( day 0 ) . The 1-year overall survival rate for all patients is 67 % ( median follow-up 29 months ) . For the 24 patients with cisplatin-sensitive disease , the 1-year overall and event-free survivals are 88 and 64 % , respectively . For those with cisplatin refractory or absolutely refractory disease , the 1-year overall survival is 25 % . In all , 12 patients relapsed at a median duration of 5 months , 11 of whom have died . There were also six treatment-related deaths , five associated with pneumonitis . Pulmonary toxicity has been reported with paclitaxel in other high-dose regimes . Since altering our protocol so that paclitaxel is infused over 24 h with steroid prophylaxis , only one of 18 patients ( 13 testicular GCTs and five other tumour types ) has had a treatment-related death . Our results suggest that Carbop-EC-T may enable a greater proportion of patients with relapsed and refractory GCTs to enter long-term remission We evaluated high-dose carboplatin and etoposide with autologous bone marrow stem cell support in the salvage treatment of patients with metastatic germ cell tumours who had failed previous chemotherapy . The treatment programme comprised initial conventional dose chemotherapy .  23 patients received a first cycle of high-dose treatment , and 12 who showed no evidence of progression had a second cycle 2 - 3 months later . 8 of the 23 patients treated with high-dose chemotherapy are alive in remission 4 - 29 months from the start of high-dose treatment . 3 of these 8 required further treatment for recurrence . In the initial part of the study , the dose of carboplatin was escalated in successive patients . Grade 3/4 treatment-related toxicity occurred in 4 of 18 patients ( 1 fatal ) who received carboplatin doses to give a AUC ( area under the serum concentration/time curve ) of 30 mg.min/ml or less and 3 of 5 patients ( 2 fatal ) who received higher doses . We , therefore , recommend 30 mg.min/ml for further evaluation in chemotherapy sensitive patients PURPOSE To study feasibility and efficacy of a new salvage regimen in patients with relapsed and /or refractory germ cell tumors . PATIENTS AND METHODS Between May 1995 and February 1997 , 80 patients were entered onto a phase II study . Conventional-dose salvage treatment with three cycles of paclitaxel 175 mg/m(2 ) , ifosfamide 5 x 1.2 g/m(2 ) , and cisplatin 5 x 20 mg/m(2 ) ( TIP ) was followed by one cycle of high-dose chemotherapy ( HDCT ) with carboplatin 500 mg/m(2 ) x 3 , etoposide 600 mg/m(2 ) x 4 , and thiotepa 150 to 250 mg/m(2 ) x 3 ( CET ) . In 23 patients , one additional cycle of paclitaxel 175 mg/m(2 ) and ifosfamide 5 g/m(2 ) ( TI ) was given immediately before TIP to improve stem-cell mobilization . RESULTS Fifty-five ( 69 % ) of 80 patients responded to TIP , 24 ( 30 % ) of 80 patients had stable disease ( n = 5 ) or tumor progression ( n = 19 ) , and one patient died . Only 62 ( 78 % ) of 80 patients received subsequent HDCT . Among those , 41 ( 66 % ) of 62 patients responded and 20 ( 32 % ) of 62 patients had stable disease ( n = 3 ) or tumor progression ( n = 17 ) . One patient died after HDCT from multiorgan failure . Survival probabilities at 3 years were 30 % for overall and 25 % for event-free survival . Peripheral neurotoxicity with sensorimotor impairment grade 2 through 4 in 29 % , paresthesias grade 2 through 4 in 24 % , and skin toxicity grade 2 through 3 in 15 % of patients were the most relevant side effects . CONCLUSION Treatment with TIP followed by high-dose CET is feasible and can induce long-term remissions in 25 % of patients with relapsed or refractory germ cell tumors . Peripheral nervous toxicity in approximately one third of patients is a disadvantage of this salvage strategy BACKGROUND Incomplete remission or relapse from first-line chemotherapy has poor prognosis in male germ cell tumour patients . This phase III r and omised trial compares conventional salvage to high-dose-intensification chemotherapy . PATIENTS AND METHODS Between February 1994 and September 2001 , 280 patients from 43 institutions in 11 countries , were r and omly assigned to receive either four cycles of cisplatin , ifosfamide and etoposide ( or vinblastine ) ( arm A ) , or three such cycles followed by high-dose carboplatin , etoposide and cyclophosphamide ( CarboPEC ) with haematopoietic stem cell support ( arm B ) . RESULTS Similar complete and partial response rates were observed in both treatment arms ( 56 % ; 95 % CI 50 % to 62 % ) . There were 3 % and 7 % toxic deaths in arms A and B , respectively . No significant improvements with CarboPEC were observed in either 3-year event-free survival ( 35 % versus 42 % , P=0.16 ) or overall survival ( 53 % ; 95 % CI 46 % to 59 % ) . Complete responders with CarboPEC had a significant improvement in disease-free survival ( 55 % versus  
    Output:
    