Amifostine

Amifostine is a cytoprotective adjuvant used in cancer chemotherapy involving DNA-binding chemotherapeutic agents. It is marketed by MedImmune under the trade name Ethyol. more...

Amifostine is used therapeutically to reduce the incidence of neutropenia-related fever and infection induced by DNA-binding chemotherapeutic agents including alkylating agents (e.g. cyclophosphamide) and platinum-containing agents (e.g. cisplatin). It is also used to decrease the cumulative nephrotoxicity associated with platinum-containing agents. Amifostine is also indicated to reduce the incidence of xerostomia in patients undergoing radiotherapy for head and neck cancer.

Of note, amifostine was originally indicated to reduce the cumulative renal toxicity from cisplatin in non-small cell lung cancer. However, while nephroprotection was observed, the fact that amifostine could protect tumors could not be excluded. Given better treatment options for non-small cell lung cancer, this indication for non-small cell lung cancer was withdrawn in 2005.

Amifostine is an organic thiophosphate prodrug which is dephosphorylated in vivo by alkaline phosphatase to the active cytoprotective thiol metabolite. The selective protection of non-malignant tissues is believed to be due to higher alkaline phosphatase activity, higher pH, and vascular permeation of normal tissues.

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