Personalised chemotherapy based on tumour marker decline in poor prognosis germ-cell tumours (GETUG 13): a phase 3, multicentre, randomised trial

摘要: Summary Background Poor prognosis germ-cell tumours are only cured in about half of patients. We aimed to assess whether treatment intensification based on an early tumour marker decline will improve progression-free survival for patients with tumours. Methods In this phase 3, multicentre, randomised trial, were enrolled from France (20 centres), USA (one centre), and Slovakia centre). Patients eligible if they older than 16 years, had evidence testicular, retroperitoneal, or mediastinal non-seminomatous germ cell histological findings clinical highly elevated serum human chorionic gonadotropin alfa-fetoprotein concentrations that matched International Germ Cell Cancer Consensus Group poor criteria. After one cycle BEP (intravenous cisplatin [20 mg/m 2 per day 5 days], etoposide [100 intramuscular intravenous bleomycin [30 mg days 1, 8, 15]), patients' measured at 18–21. a favourable continued (Fav-BEP group) 3 additonal cycles, whereas unfavourable randomly assigned (1:1) receive either (Unfav-BEP dose-dense regimen (Unfav-dose-dense group), consisting paclitaxel (175 over h 1) before plus oxaliplatin (130 10; two cycles), followed by (100 1), ifosfamide (2 g/m 10, 12, 14), mesna (500 0, 7 11 h), (25 units day, continuous infusion 10–14; granulocyte-colony stimulating factor (lenograstim) support. Centrally blocked computer-generated randomisation stratified centre was used. The primary endpoint the efficacy analysis done intention-to-treat population. planned trial accrual completed May, 2012, follow-up is ongoing. This study registered ClinicalTrials.gov, number NCT00104676. Findings Between Nov 28, 2003, May 16, 263 254 available assessment. Of these 51 (20%) assessment, 203 (80%) decline; 105 Unfav-dose-dense group 98 Unfav-BEP group. 3-year 59% (95% CI 49–68) versus 48% (38–59) (HR 0·66, 95% 0·44–1·00, p=0·05). 70% 57–81) Fav-BEP 0·49–0·88, p=0·01 compared group). More grade 3–4 neurotoxic events (seven [7%] vs [1%]) haematotoxic occurred group; there no difference 1–2 febrile neutropenia (18 [17%] 18 [18%]) toxic deaths [1%] both groups). Salvage high-dose chemotherapy stem-cell transplant required six (6%) (16%) Interpretation Personalised reduces risk progression death decline. Funding Institut National du (Programme Hospitalier de Recherche Clinique).