Cyclophosphamide versus ifosfamide: "To use ifosfamide or not to use, thatis the three-dimensional question"

Ifosfamide and cyclophosphamide are alkylating agents that are extensively used in the clinical treatment of cancer. However, the continued use of ifo sfamide has been questioned with the suggestion that cyclophosphamide be us ed exclusively. One response to this proposal is based upon the fact that b oth cyclophosphamide and isfosfamide are chiral and are administered as rac emic (50:50) mixtures of the two isomers. Studies of the clinical pharmacol ogy, metabolism and disposition of these agents indicate that stereochemist ry plays a minor role in the efficacy and toxicity of cyclophosphamide but is a major factor in neurotoxicity associated with ifosfamide administratio n. 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 ne urotoxicity, (S)-ifosfamide.