amifostine

Amifostine is a sulphydryl antioxidant compound. It has been shown to protect certain normal tissues from the toxic effects of radiotherapy and several cytotoxic drugs, both in animal models and clinical studies.

Amifostine is believed to scavenge free radicals, disarm radicals on membranes and DNA, and form mixed disulphides to protect normal cells.

The selectivity, in terms of protection of normal tissues, is assumed to be connected to the perfusion-related distribution and absorption of amifostine, and a greater alkaline-phophatase activity in normal tissues than in malignant tissues.

Extensive uptake is seen in salivary glands, kidneys and intestinal mucosa, whereas markedly lower uptake is seen in tumour tissues and some other normal tissues. It has been assumed that amifostine is an inactive prodrug that is preferentially activated by alkaline phosphatase in normal tissues.

Amifostine was recently approved for use in head and neck cancer to protect against radiation-induced XEROSTOMIA. The question has arisen as to whether amifostine could be used for radioprotection in broader terms, or even extended into chemoprotection.

It is well documented that clinically relevant radioprotection can be achieved in salivary glands with amifostine. However, because of the uneven protection offered to different normal tissues, it seems unlikely that an escalation of radiation dose will be possible with amifostine.

See also

 chemoprotection