Pharmacologic normal tissue protection in clinical radiation oncology: focus on amifostine

Mell, Loren K.; Movsas, Benjamin

doi:10.1517/17425255.4.10.1341

Cited by 19 publications

(5 citation statements)

References 70 publications

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“…In this regard, ROS, as early drivers of mucosa damage, represent a potential target for the inhibition of mucositis development. Antioxidant agents, such as amifostine, have been found to partially prevent mucositis development during RT treatment, reducing DNA strand breaks and preserving salivary gland, endothelium and connective tissue integrity [65,66]. However, the related adverse events and the intravenous administration limit amifostine use in the routine clinical practice.…”

Section: Antioxidant Agentsmentioning

confidence: 99%

Oral mucositis: the hidden side of cancer therapy

Pulito¹,

Cristaudo

Porta

et al. 2020

J Exp Clin Cancer Res

245

135

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Inflammation response of epithelial mucosa to chemo- radiotherapy cytotoxic effects leads to mucositis, a painful side effect of antineoplastic treatments. About 40% of the patients treated with chemotherapy develop mucositis; this percentage rises to about 90% for head and neck cancer patients (HNC) treated with both chemo- and radiotherapy. 19% of the latter will be hospitalized and will experience a delay in antineoplastic treatment for high-grade mucositis management, resulting in a reduction of the quality of life, a worse prognosis and an increase in patient management costs. Currently, several interventions and prevention guidelines are available, but their effectiveness is uncertain. This review comprehensively describes mucositis, debating the impact of standard chemo-radiotherapy and targeted therapy on mucositis development and pointing out the limits and the benefits of current mucositis treatment strategies and assessment guidelines. Moreover, the review critically examines the feasibility of the existing biomarkers to predict patient risk of developing oral mucositis and their role in early diagnosis. Despite the expression levels of some proteins involved in the inflammation response, such as TNF-α or IL-1β, partially correlate with mucositis process, their presence does not exclude others mucositis-independent inflammation events. This strongly suggests the need to discover biomarkers that specifically feature mucositis process development. Non-coding RNAs might hold this potential.

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Section: Antioxidant Agentsmentioning

confidence: 99%

Oral mucositis: the hidden side of cancer therapy

Pulito¹,

Cristaudo

Porta

et al. 2020

J Exp Clin Cancer Res

245

135

View full text Add to dashboard Cite

show abstract

“…RISGI is closely related to free radicals produced by radiotherapy. As a free radical scavenger, amifostine can effectively reduce the SG damage caused by radiation [ 70 , 71 ]. At first, amifostine is effective in reducing oral problems caused by salivary dysfunction after radiotherapy (tooth caries, oral candidiasis, and mucositis) [ 72 , 73 , 74 ].…”

Section: Treatment Of Risgimentioning

confidence: 99%

Mechanism, Prevention, and Treatment of Radiation-Induced Salivary Gland Injury Related to Oxidative Stress

et al. 2021

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Radiation therapy is a common treatment for head and neck cancers. However, because of the presence of nerve structures (brain stem, spinal cord, and brachial plexus), salivary glands (SGs), mucous membranes, and swallowing muscles in the head and neck regions, radiotherapy inevitably causes damage to these normal tissues. Among them, SG injury is a serious adverse event, and its clinical manifestations include changes in taste, difficulty chewing and swallowing, oral infections, and dental caries. These clinical symptoms seriously reduce a patient’s quality of life. Therefore, it is important to clarify the mechanism of SG injury caused by radiotherapy. Although the mechanism of radiation-induced SG injury has not yet been determined, recent studies have shown that the mechanisms of calcium signaling, microvascular injury, cellular senescence, and apoptosis are closely related to oxidative stress. In this article, we review the mechanism by which radiotherapy causes oxidative stress and damages the SGs. In addition, we discuss effective methods to prevent and treat radiation-induced SG damage.

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“…AMF (Ethyol ® ) administered to cancer patients is rapidly cleared from plasma by a biphasic decay with an alpha half-life (T1/2α) of 0.88 min and a T1/2β of 8.8 min [ 1 ]. Therefore, AMF is administered to patients as a 15 min intravenous infusion before cisplatin and carboplatin administration to protect against dose-limiting toxicities [ 1 , 5 ]. However, AMF continues to be evaluated as a cytoprotector in other clinical settings involving radiotherapy and chemotherapy [ 2 , 6 , 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

Preparation and Evaluation of Inhalable Amifostine Microparticles Using Wet Ball Milling

et al. 2023

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The conventional dosage form of Ethyol® (amifostine), a sterile lyophilized powder, involves reconstituting it with 9.7 mL of sterile 0.9% sodium chloride in accordance with the United States Pharmacopeia specifications for intravenous infusion. The purpose of this study was to develop inhalable microparticles of amifostine (AMF) and compare the physicochemical properties and inhalation efficiency of AMF microparticles prepared by different methods (jet milling and wet ball milling) and different solvents (methanol, ethanol, chloroform, and toluene). Inhalable microparticles of AMF dry powder were prepared using a wet ball-milling process with polar and non-polar solvents to improve their efficacy when delivered through the pulmonary route. The wet ball-milling process was performed as follows: AMF (10 g), zirconia balls (50 g), and solvent (20 mL) were mixed and placed in a cylindrical stainless-steel jar. Wet ball milling was performed at 400 rpm for 15 min. The physicochemical properties and aerodynamic characteristics of the prepared samples were evaluated. The physicochemical properties of wet-ball-milled microparticles (WBM-M and WBM-E) using polar solvents were confirmed. Aerodynamic characterization was not used to measure the % fine particle fraction (% FPF) value in the raw AMF. The % FPF value of JM was 26.9 ± 5.8%. The % FPF values of the wet-ball-milled microparticles WBM-M and WBM-E prepared using polar solvents were 34.5 ± 0.2% and 27.9 ± 0.7%, respectively; while the % FPF values of the wet-ball-milled microparticles WBM-C and WBM-T prepared using non-polar solvents were 45.5 ± 0.6% and 44.7 ± 0.3%, respectively. Using a non-polar solvent in the wet ball-milling process resulted in a more homogeneous and stable crystal form of the fine AMF powder than using a polar solvent.

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Pharmacologic normal tissue protection in clinical radiation oncology: focus on amifostine

Cited by 19 publications

References 70 publications

Oral mucositis: the hidden side of cancer therapy

Oral mucositis: the hidden side of cancer therapy

Mechanism, Prevention, and Treatment of Radiation-Induced Salivary Gland Injury Related to Oxidative Stress

Preparation and Evaluation of Inhalable Amifostine Microparticles Using Wet Ball Milling

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