Cyclophosphamide versus ifosfamide: to use ifosfamide or not to use, that is the three-dimensional question

Abstract

Ifosfamide and cyclophosphamide are alkylating agents that are extensively used in the clinical treatment of cancer. However, the continued use of ifosfamide has been questioned with the suggestion that cyclophosphamide be used exclusively. One response to this proposal is based upon the fact that both cyclophosphamide and isfosfamide are chiral and are administered as racemic (50:50) mixtures of the two isomers. Studies of the clinical pharmacology, metabolism and disposition of these agents indicate that stereochemistry plays a minor role in the efficacy and toxicity of cyclophosphamide but is a major factor in neurotoxicity associated with ifosfamide administration. Studies have demonstrated that the use of a single ifosfamide enantiomer, (R)-ifosfamide would retain the unique antitumor efficacy of this agent, while eliminating the major source of the observed ifosfamide-associated neurotoxicity, (S)-ifosfamide.