The role of ifosfamide in the treatment of lymphomas

Over the last few decades, progress has been made in classification and treatment guidelines for patients with lymphoma with differing prognostic factors. As investigators look for alternatives to current standard therapy there has been a resurgence of interest in the alkylating agent ifosfamide. A basic tenet of lymphoma therapy has been to use combinations of non-cross resistant agents in an effort to avoid tumor resistance. Ifosfamide is at least partially non-cross resistant with cyclophosphamide, and because it is often only modestly myelosuppressive, it is useful in combination regimens. Other toxicities of ifosfamide, including urinary bladder toxicity and neurotoxicity, are generally predictive and seldom occur in clinical practice with standard ifosfamide doses and proper screening and preventive therapy. Several regimens incorporating ifosfamide in a variety of doses and schedules have demonstrated clinical efficacy in the treatment of lymphomas. Ifosfamide is most commonly used in regimens for patients with relapsed or refractory disease, although there has been interest in ifosfamide as part of initial therapy regimens. Ifosfamide is an active agent as part of combination therapy for patients with both indolent and aggressive relapsed lymphomas, and has also been used in high-dose therapy regimens followed by stem cell or bone marrow rescue. Future studies incorporating ifosfamide should be directed towards its use in outpatient regimens as initial therapy for patients with lymphoma and in regimens designed for patients with relapsed or refractory disease.