The efficacy and safety of amifostine for the acute radiation syndrome

Abstract

Introduction: A radiation countermeasure that can be used prior to radiation exposure to protect the population from the harmful effects of radiation exposure remains a major unmet medical need and is recognized as an important area for research. Despite substantial advances in the research and development for finding nontoxic, safe, and effective prophylactic countermeasures for the acute radiation syndrome (ARS), no such agent has been approved by the United States Food and Drug Administration (FDA). Area covered: Despite the progress made to improve the effectiveness of amifostine as a radioprotector for ARS, none of the strategies have resolved the issue of its toxicity/side effects. Thus, the FDA has approved amifostine for limited clinical indications, but not for non-clinical uses. This article reviews recent strategies and progress that have been made to move forward this potentially useful countermeasure for ARS. Expert opinion: Although the recent investigations have been promising for fielding safe and effective radiation countermeasures, additional work is needed to improve and advance drug design and delivery strategies to get FDA approval for broadened, non-clinical use of amifostine during a radiological/nuclear scenario. ARTICLE HISTORY

Comparative proteomic analysis of serum from nonhuman primates administered BIO 300: a promising radiation countermeasure

“…Amifostine and palifermin are two other FDA approved radioprotectants that act as cytoprotective agents and are also associated with serious side effects 9 , 10 . Researchers have demonstrated the potential toxicity and lethality of using high doses of amifostine 10 – 13 . Clearly there is a need for new and effective medical countermeasures against radiation exposure.…”

“…require close patient monitoring upon administration 7,8 . Amifostine and palifermin are two other FDA approved radioprotectants that act as cytoprotective agents and are also associated with serious side effects 9,10 . Researchers have demonstrated the potential toxicity and lethality of using high doses of amifostine [10][11][12][13] .…”

Epitaxially Strained CeO2/Mn3O4 Nanocrystals as an Enhanced Antioxidant for Radioprotection

“…[ 2 ] Although Amifostine (Ethyol) was developed as a radioprotectant, [ 3 ] its application is only approved for the protection of salivary glands, because its short elimination half‐life and limited ROS‐scavenging capacity require a high dose, which may cause systemic toxicity and complications, to be used under TBI conditions. [ 4 ] In light of this, long‐lasting radioprotectants with improved ROS‐scavenging activities are highly desired.…”

Pharmacological management of ionizing radiation injuries: current and prospective agents and targeted organ systems

“…Based on existing information from other radiation countermeasures, it was a logical approach to test whether amifostine could enhance the radioprotective efficacy of other radiation countermeasures that act through a different pathway or if the efficacy of amifostine could be improved by another agent. Amifostine has been tried with several growth factors and other agents while under development as a radiation countermeasure [199]. Some of the agents which have been combined with amifostine or its derivatives to improve efficacy are G-CSF, metformin, selenium, vitamin-E, gamma-tocotrienol, prostaglandin E2, β-glucan, and roncho-Vaxom [199].…”

“…Amifostine has been tried with several growth factors and other agents while under development as a radiation countermeasure [199]. Some of the agents which have been combined with amifostine or its derivatives to improve efficacy are G-CSF, metformin, selenium, vitamin-E, gamma-tocotrienol, prostaglandin E2, β-glucan, and roncho-Vaxom [199]. Similarly, there are reports for the combination of flagellin and IL-1β [200], gamma-tocotrienol and Simvastatin/pentoxifylline [201,202], filgrastim and α-tocopherol succinate [203], and PEGfilgrastim and Romiplostim [73].…”