Radioprotectors and normal-tissue sparing drugs
Drugs that shield healthy tissue from radiation: amifostine to protect salivary glands, palifermin for mouth ulcers, and newer agents aimed at the gut, lung and skin.
Overview
Amifostine, a thiol prodrug, was approved to reduce dry mouth after head and neck radiotherapy and kidney damage from cisplatin, but nausea, low blood pressure and worries about tumour protection limited its use; intensity-modulated radiotherapy achieved the same salivary sparing by physics. Palifermin, a keratinocyte growth factor, reduces severe mucositis after total body irradiation. Research continues on agents that protect the gut and lung, on mitigators given after exposure (relevant to radiation accidents as well as therapy), and on drugs that separate tumour and normal tissue response such as avasopasem.
How it works
Free-radical scavenging, growth factor support or selective protection of normal cells reduces radiation injury without shielding the tumour.
- Reduces specific toxicities
- Complements physical sparing
- Mitigators can be given after exposure
- Side effects of the protector itself
- Possible tumour protection
- Few agents have shown clear clinical benefit
Avasopasem is Galera Therapeutics' radioprotector for the severe mouth ulcers of head and neck chemoradiation; its phase 3 trial met its main goal but the FDA asked for another study in 2023.
Pilocarpine tablets are approved to treat the dry mouth that follows head and neck radiotherapy; they help when some gland tissue is left, at the cost of sweating and other cholinergic side effects.
Latest papers
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