Dosing considerations with amifostine: A review of the literature and clinical experience

Numerous dosing regimens have been used in the clinical development of amifostine (Ethyol; Alza Pharmaceuticals, Palo Alto, CA/US Bioscience, West Conshohocken, PA). Whereas the current recommended dose of amifostine is 910 mg/m² administered intravenously as a 15-minute infusion 30 minutes before chemotherapy, other studies have demonstrated cytoprotection with lower doses, suggesting that the optimal biologic dose may indeed be lower. Amifostine doses that protect against the toxicities associated with daily fractionated radiotherapy are also lower, with a dose range of 200 to 340 mg/m² per fraction commonly reported in the literature. The toxicities most commonly associated with amifostine, namely, hypotension and nausea and vomiting, are dose related. They can be reduced using adequate prophylactic measures and can be effectively managed if they occur. Hypocalcemia and allergic reactions also can be lessened or averted with precautionary measures. Thus, although amifostine is generally well tolerated at the current recommended doses, clinical studies of variations in the approved dosing regimen would be useful in further defining the optimal amifostine dose for chemoprotection, for radioprotection, and for inducing hematopoiesis in patients with refractory myelodysplastic syndromes.