Palifosfamide, a bifunctional alkylator for the treatment of sarcomas

Ifosfamide is a chemotherapeutic prodrug used in the treatment of several tumor entities, including bone and soft-tissue sarcoma. However, the application of high-dose ifosfamide is not feasible because of severe side effects caused by metabolites. The active metabolite isophosphoramide mustard is not suitable for administration because of chemical instability. ZIOPHARM Oncology Inc, under license from Dekk-Tec Inc, is developing palifosfamide, a formulation of isophosphoramide mustard with tris(hydroxymethyl)aminomethane salt-stabilization (palifosfamide-tris) and previously with lysine-stabilization (palifosfamide-lys). Preclinical studies and phase I and I/II clinical trials demonstrated that palifosfamide-tris had an antitumor efficiency comparable or superior to that of ifosfamide. Patients treated with palifosfamide-tris did not display any of the neurotoxic or nephrotoxic side effects associated with ifosfamide. At the time of publication, data from phase II trials were being evaluated and phase III trials were being planned. palifosfamide-tris is expected to be a safer and less toxic alternative to ifosfamide; however, considering other new approaches under investigation for tumors such as sarcoma, such as molecular-based treatment strategies, it is unclear what position palifosfamide-tris might occupy on the market.