Question: Can we use prodrug amifostine to protect healthy cell during chemotherapy?

Context:
CYP), a commonly prescribed chemotherapy drug, has multiple adverse side effects including alteration of taste. The effects on taste are a cause of concern for patients as changes in taste are often associated with loss of appetite, malnutrition, poor recovery and reduced quality of life. Amifostine is a cytoprotective agent that was previously shown to be effective in preventing chemotherapy-induced mucositis and nephrotoxicity.
In vivo mesna and amifostine do not prevent chloroacetaldehyde nephrotoxicity in vitro
Amifostine protects bone marrow from benzene-induced hematotoxicity in mice.
Amifostine treatment in benzene-exposed mice significantly improved blood cell counts, and morphological and histopathological signs of hematotoxicity in the bone marrow as well as in the spleen. Moreover, amifostine prevented benzene-induced bone marrow and spleen cell apoptosis and rescinded the inhibition of cell proliferation induced by benzene exposure. Finally, amifostine significantly inhibited the levels of reactive oxidative species and lipid peroxidation induced by benzene exposure.
Amifostine-antioxidant drug in anticancer therapy.
. Amifostine alone is inactive chemically, but active metabolite amifostine WR-1065 has been assumed to protect the healthy tissues during antineoplastic therapy by bounding of anticancer drug, causing their detoxification and/or eliminating the free radicals generated during radiation and cytostatic therapy
Doxorubicin induces apoptosis in germ line stem cells in the immature rat testis and amifostine cannot protect against this cytotoxicity
Amifostine was developed to protect normal tissues from radiation exposure
(AMF) has been shown to protect some normal tissues from acute effects of radiation therapy +/- chemotherapy
Amifostine has been shown to protect against xerostomia induced by radiotherapy for head and neck cancer, but its impact on the therapeutic index is unknown. This is the first report focusing on amifostine related adverse effects leading to discontinuation of amifostine treatment.
Amifostine inhibits angiogenesis in vivo
Amifostine has shown to selectively protect normal tissues against cytotoxic and mutagenic effects of several anti-neoplastic drugs, such as alkylating agents, organoplatinum compounds, anthracyclines, taxanes, and ionising radiati
Amifostine (Ethyoltrade mark, Alza Pharmaceuticals) is an inorganic thiophosphate cytoprotective agent known chemically as ethanethiol, 2-[3- aminopropyl)amino]dihydrogen phosphate. It is a prodrug of free thiol (WR-1065) that may act as a scavenger of free radicals generated in tissues exposed to cytotoxic drugs and binds to reactive metabolites of such drugs. Amifostine was originally developed as a radioprotective agent in a classified nuclear warfare project
Preclinical studies demonstrate that amifostine has the potential to selectively protect normal tissues from the harmful effects of radiation without significantly protecting neoplastic tissue. The potential value of such an agent includes reducing treatment-related toxicity and the opportunity for radiation dose escalation in the curative treatment of cancer. An increasing number of human clinical trials have been conducted that define the toxicity profile and efficacy of radioprotection by amifostine when used during fractionated radiation therapy
Radioprotective effects of amifostine.

Answer: Effective radiotherapy for patients with cancer should include maximal tumor cell killing with minimal injury to normal tissue. However, current radiation doses that can be delivered without causing severe damage to surrounding normal tissues are often insufficient to eradicate a tumor. Recently, a number of agents have been developed to protect normal tissue from the harmful effects of antitumor therapies. The aminothiol amifostine (Ethyol; Alza Pharmaceuticals, Palo Alto, CA/US Bioscience, West Conshohocken, PA) has been the subject of extensive research as a prospective protector. While this drug has been approved for use to reduce toxicities associated with cisplatin, several studies also have demonstrated that amifostine protects normal tissues from both acute and late radiation damage without protecting the tumor. Consequently, higher radiation doses could be used with less than or equal risk to surrounding normal tissues.