Has the outlook improved for amifostine as a clinical radioprotector?

Amifostine has recently been approved for clinical radiotherapy as a protector against irradiation-induced xerostomia. It is our aim to review the outlook for using amifostine as a general clinical radioprotector. Protection against X-rays is mainly obtained by the scavenging of free radicals. The degree of protection is therefore highly dependent on oxygen tension, with protection factors ranging from 1 to 3. Maximal protection is observed at physiological levels of oxygenation. A great variability in protection has also been observed between different normal tissues. Some tissue, like brain, is not protected while salivary glands and bone marrow may exhibit a three-fold increase in radiation tolerance. Amifostine is dephosphorylized to its active metabolite by a process involving alkaline phosphatase. Due to lower levels of alkaline phosphatase in tumor vessels, amifostine is marketed as a selective protector of normal tissue and not tumors. However, the preclinical investigations concerning the selectivity of amifostine are controversial and the clinical studies are sparse and do not have the power to evaluate the influence of amifostine on the therapeutic index. Conclusion: based on the present knowledge amifostine should only be used in experimental protocols and not in routine practice. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.