Mafosfamide as a new anticancer agent: preclinical investigations and clinical trials.

Mafosfamide (4-thioethane sulfonic acid salt of 4-hydroxy-cyclophosphamide, MAF) belongs to a new generation of the oxazaphosphorine agents. MAF is a cyclophosphamide analog which spontaneously degrades to 4-hydroxy-cyclophosphamide. The effects of MAF on various types of cancer cells were determined during preclinical investigations and clinical trials. The positive results from in vitro and in vivo anticancer studies promoted MAF to a good candidate for phase I trials. Clinical experience with intrathecal MAF, used for patients with neoplastic meningitis due to leukemia, lymphoma, and solid tumors, indicated good tolerability and efficacy. The recommended phase II doses of intrathecally administered MAF were determined. Clinical trials using intrathecal MAF are now underway. To obtain a better therapeutic index, a strategy to alternate dosing between the intraventricular and intralumbar routes is also being tested. MAF is an attractive agent for regional cancer therapy. The current available knowledge on MAF as a new anticancer agent is based on a collection of the original published studies, conference abstracts and relevant articles.