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Background: Poor-prognosis GCT(IGCCCG,J Clin Oncol 1997)remains a challenge with no improvement in the 50%survival demonstrated in phase Ⅲ trials for 25 years.Day 21 serum tumor marker decline rate identified a subgroup of patients(pts)with a better outcome(J Clin Oncol 2004,22: 3868-76).The hypothesis we tested in this study is that treatment allocation based on early tumor marker decline will improve the progression-free survival(PFS).Methods: Pts with IGCCCG poor-prognosis GCT were treated with a first cycle of BEP.AFP and hCG were assessed at day 18–21: 1)Pts with a favorable decline continued BEP for a total of 4 courses(Fav-BEP); 2)Pts with an unfavorable decline were randomized to receive either BEP(Unfav-BEP)or a dose-dense regimen(Unfav-dose-dense),consisting of paclitaxel-BEP plus day-10 oxaliplatin x 2 cycles,followed by 2 cycles of cisplatin,ifosfamide,and continuous infusion bleomycin(depending on lung function)+ G-CSF.The primary endpoint was PFS(hypothesis: 20%difference,type 1 error: 5%,power 80%,196 randomized pts needed).Results: 263 pts were enrolled and 254 were evaluable at day 21(6 early deaths,3 withdrawals): 51 pts(20%)had favorable tumor marker decline and 203 had unfavorable decline(randomized: 105 Unfav-dose-dense arm,98 Unfav-BEP).The prognostic value of early tumor marker decline(Fav-BEP vs Unfav-BEP)was confirmed: 70%vs 48%for 3-year PFS(p=0.01),and 84%vs 65%for overall survival(OS)(p=0.02).The 3-year PFS was 59%in the Unfav-dose-dense arm vs 48%in the Unfav-BEP arm(p=0.05; HR: 0.66 [0.44-1.00]).3-year OS was 73%and 65%,respectively.More ≥ grade 2 neurotoxicity(21%vs 4%)and more hematotoxicity occurred in the dose-dense arm,with no excess febrile neutropenia(17%each arm)or toxic deaths(1 each arm).Salvage high-dose chemotherapy + stem-cell transplant were required in 6%in the Unfav-dose-dense arm and 16%in the Unfav-BEP arm(p=0.01).Conclusions: An algorithm of individualized treatment intensification determined by the rate of early tumor marker decline reduces the risk of progression or death in men with poor-prognosis GCT.