High-dose chemotherapy and autologous bone marrow transplantation for patients with poor prognosis nonseminomatous germ cell tumours

Abstract

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 candidemia 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 standard therapy may allow cure to be a realistic expectation.