***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 
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    Input: Twenty-one patients with poor prognosis nonseminomatous germ cell tumours ( six with extreme burden disease at presentation in whom partial remission had been achieved with initial induction therapy , and 15 with recurrent disease after induction therapy ) were treated with high-dose chemotherapy and autologous bone marrow transplantation ( BMT ) . The first six received etoposide 3.0 g m-2 , ifosfamide 6.0 g m-2 and carboplatin 1.2 g m-2 ( Regimen 1 ) , and the subsequent 15 received etoposide 2.4 g m2 ( continuous infusion ) , cyclophosphamide 7.2 g m-2 and carboplatin 0.8 g m-2 ( Regimen 2 ) followed by infusion of previously stored autologous marrow . Regimen 1 was associated with considerable renal toxicity and mucositis , whereas Regimen 2 was relatively well tolerated . Two patients died as a consequence of the treatment : one of c and idemia and one of interstitial pulmonary fibrosis . Only one of 17 patients who were autografted in or approaching marker remission subsequently developed disease progression ( event-free survival 82 % , 95 % confidence interval [ CI ] 55 % to 94 % ) , whereas all four patients who had progressive disease at autografting subsequently developed further disease progression and died . Fourteen patients remain well and free of disease 0.5 to 6.5 years ( median 3.3 ) post-BMT ( event-free survival 67 % , 95 % CI 43 % to 83 % ) . A strategy of prompt reinduction followed by high-dose chemotherapy and autologous BMT at the first sign of failure of st and ard therapy may allow cure to be a realistic expectation PURPOSE To evaluate the optimal dose of carboplatin as well as the efficacy and tolerability of sequential , dose-intense chemotherapy with paclitaxel and ifosfamide followed by carboplatin and etoposide ( TICE ) plus peripheral-blood stem-cell ( PBSC ) support in patients with germ cell tumors ( GCT ) who are likely to experience treatment failure with conventional-dose salvage treatment . This prospect i ve trial followed a similarly design ed report of TICE , which used a different means of carboplatin dosing . PATIENTS AND METHODS The 48 patients entered onto this trial had progressive GCT and unfavorable prognostic features after chemotherapy . Two cycles of paclitaxel plus ifosfamide were administered with leukapheresis , followed by three cycles of carboplatin plus etoposide with reinfusion of PBSC . RESULTS Twenty-three ( 49 % ) of 47 assessable patients achieved a complete response ( CR ) to chemotherapy . An additional three patients ( 6 % ) achieved a CR to chemotherapy and surgery . The CR rate was 55 % . Six patients experienced relapse , but 24 patients ( 51 % ) are alive and free of disease at a median follow-up time of 40 months . Four patients who experienced relapse or achieved an incomplete response were rendered disease free by salvage surgical resection . When combined with results of the prior trial of similar design , TICE chemotherapy yielded an overall CR of 56 % ( n = 84 ) , with 50 % of patients alive with no evidence of disease . CONCLUSION TICE is an effective and tolerable dose-intense treatment for patients with previously treated metastatic GCT who have a poor predicted outcome to conventional-dose salvage chemotherapy Between April 1984 and May 1985 , 17 heavily pretreated patients with relapsing or refractory germ cell tumours were treated with cisplatin 40 mg/m2/day , days 1 - 5 ; etoposide 350 mg/m2/day , days 1 - 5 ; cyclophosphamide 1600 mg/m2/day , days 2 - 5 and autologous bone marrow transplantation on day 8 as consolidation of conventional salvage chemotherapy . None of the 11 refractory patients and 4 of the 6 responders to prior salvage treatment are long-term survivors at 68 , 72 , 74 and 74 months . Mean aplasia duration was 17 days and there were 7 documented episodes of septicaemia in 17 febrile patients . 1 patient died of treatment . Among the 4 survivors , 2 patients have a sustained grade II invalidating neuropathy . We conclude that this regimen is not recommended as salvage therapy in refractory patients but may be a useful consolidation treatment in patients responding to conventional salvage chemotherapy BACKGROUND In the late 1990s , the use of high-dose chemotherapy ( HDCT ) and stem-cell rescue held promise for patients with advanced and poor prognosis germ-cell tumors ( GCT ) . We started a r and omized phase II trial to assess the efficacy of sequential HDCT compared with cisplatin , etoposide , and bleomycin ( PEB ) . PATIENTS AND METHODS Patients were r and omly assigned to receive four cycles of PEB every 3 weeks or two cycles of PEB followed by a high-dose sequence ( HDS ) comprising HD-cyclophosphamide ( 7.0 g/m(2 ) ) , 2 courses of cisplatin and HD-etoposide ( 2.4 g/m(2 ) ) with stem-cell support , and a single course of HD-carboplatin [ area under the curve ( AUC ) 27 mg/ml × min ] with autologous stem-cell transplant . Postchemotherapy surgery was planned on responding residual disease in both arms . The primary end point was progression-free survival ( PFS ) . The study was design ed to detect a 30 % improvement of 5-year PFS ( from 40 % to 70 % ) , with 80 % power and two-sided α at 5 % . RESULTS From December 1996 to March 2007 , 85 patients were r and omized : 43 in PEB and 42 in HDS arm . Median follow-up was 114.2 months [ interquartile range ( IQR ) : 87.7 - 165.8 ] . Complete or partial response with normal markers ( PRm- ) were obtained in 28 ( 65.1 % ) and 29 ( 69.1 % ) patients , respectively . Five-year PFS was 55.8 % [ 95 % confidence interval ( CI ) 42.8 - 72.8 ] and 54.8 % ( 95 % CI 41.6%-72.1 % ) in PEB and HDS arm , respectively ( log-rank test P = 0.726 ) . Five-year overall survival was 62.8 % ( 95 % CI 49.9 - 79.0 ) and 59.3 % ( 95 % CI 46.1 - 76.3 ) . One toxic death ( PEB arm ) was recorded . CONCLUSIONS The study failed to meet the primary end point . Furthermore , survival estimates of conventional-dose chemotherapy higher than expected should be accounted for and will likely limit further improvements in the first-line setting . CLINICAL TRIALS.GOV : NCT02161692 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 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 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 
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For newly diagnosed patients with poor prognostic predictors , a risk adjusted strategy using unfavorable tumor marker decline with initial st and ard chemotherapy regimen and upfront HDCT demonstrated improved outcomes .
Our data suggest a minimum of two HDCT cycles with ASCT should be st and ard of care for patients with RR GCC .
Failure of HDCT results in a poor prognosis with only 10 % of patients achieving lasting remission with salvage therapy