Chemical radioprotection: A critical review of amifostine as a cytoprotector in radiotherapy

Therapeutic gain in terms of change in uncomplicated tumor control probability in an ideal scenario in which a radioprotector offers selective protection to normal tissues without affecting tumor radiosensitivity. However, the therapeutic gain is potentially diminished if the radioprotector causes tumor protection or if a single-dose–limiting normal tissue is unprotected or protected to a lesser extent. TCP, tumor control probability; NTCP, normal tissue complication probability.

Metabolism of amifostine (WR-2721). Amofostine is converted to its active metabolite WR-1065 by either spontaneous dephosphorylation or by an enzymatic process involving alkaline phosphatase. Within the cell, WR-1065 is further metabolized to the symmetrical disulfide WR-33278 that has structural similarities to naturally occurring polyamines.