An aminolthiol prodrug that is dephosphorylated rapidly into a thiol.

In healthy tissues it acts as a reactive oxygen scavenger.

Radiation exerts most of its effect via the ionization of water, resulting in the formation of highly reactive free radicals that damage DNA.

Oxygen can bind to short lived free radical sites in the DNA and fixes the damage.

Sulfhydryl compounds can compete with oxygen and reduce free radical activity and exert a protective effect.

Amifostine Is formed by the addition of a phosphate group to the sulfhydryl compound, which produces a pro drug activated by membrane bound alkaline phosphatase, which dephosphorylates the pro-drug to its active sulfhydryl molecule.

Alkaline phosphatase concentration in tumor cells is low, and this provides a selective mechanism to protect normal tissues by aminofostine in preference to protecting the tumor cells.

There is increased uptake of the amifostine compound by salivary glands and kidneys.

A radio protective agent that scavenges radiation induced the free radicals.

Protects normal tissues from adverse effects of radiation in experimental models.

The drug is rapidly cleared from blood and tissues and must be deleted shortly before radiotherapy, and preferably be for each radiotherapy fraction.

Intravenous bolus drug administration can cause significant incidence of hypotension and nausea.

Subcutaneous administration of this drug simplifies drug delivery and reduces toxicity while improving bioavailability (Koukourakis M et al).

Can reduce moderate to severe xerostomia in patients receiving radiation therapy for head and neck cancer treatment (Brizel DM et al).

Daily treatment prior to radiotherapy reduces grade 2 xerostomia compared to radiotherapy alone in head and neck radiation.

In a controlled study of patients with head and neck cancer receiving conventional radiotherapy without concurrent chemotherapy randomized to receive amifostine IV 200 mg metered square daily or subcutaneous 500 mg before each fraction of radiation: no significant difference in xerostomia or other radiation toxicity endpoints appeared in between the two arms, but more hypotension was observed with the IV treatments and higher rates of skin rash and injection site pain in the subcutaneous arm. (Bardet E et al).

Does not reduce overall survival and progression free survival in patients treated with radiotherapy or chemotherapy for a variety of cancers (Bourhis J et al).

Leave a Reply

Your email address will not be published. Required fields are marked *