Dose-intensive ifosfamide for the treatment of non-Hodgkin's lymphoma

Patients with non-Hodgkin's lymphoma (NHL) who either fail to achieve or relapse following an initial complete remission have a poor prognosis with conventional salvage chemotherapy. Patients with chemotherapy-sensitive NHL have a 45% chance of long-term disease-free survival with high-dose chemotherapy and autologous bone marrow transplantation (ABMT). Patients with chemotherapy-resistant NHL have a significantly reduced chance of long-term disease-free survival. Ifosfamide, a synthetic analogue of cyclophosphamide, has been evaluated in a few small trials of high-dose chemotherapy and ABMT in lymphoma. Because of their clinical synergy, ifosfamide has been combined with carboplatin and etoposide (ICE) and given with ABMT in several phase I/II dose-escalating studies. Maximum tolerated doses of the ICE regimen in these trials are 16 to 20.1 g/m2 ifosfamide, 1.8 g/m2 carboplatin, and 1.2 to 3.0 g/m2 etoposide. Renal, central nervous system, and cardiac toxicities have precluded further dose escalation. Sequential dosing protocols, administration of high-dose chemotherapy with peripheral blood progenitor cell support, and other approaches, possibly combining current treatment options, may be necessary to further improve the long-term survival of patients with relapsed NHL.