- StatPearls [BOOK]
- BOOKStatPearls Publishing: Treasure Island (FL)
- Radiation esophagitis is inflammation of the esophagitis due to radiation. Radiation esophagitis is typically an adverse effect that develops in individuals receiving radiation cancer therapy, most c...
Radiation esophagitis is inflammation of the esophagitis due to radiation. Radiation esophagitis is typically an adverse effect that develops in individuals receiving radiation cancer therapy, most commonly for breast, lung, and other lymphomas. Symptoms present two to three weeks after initial therapy and include throat pain, dysphagia, and the sensation that food is stuck. Ethyol (amifostine) is a medication used as a radiation protector in selected populations at risk of radiation esophagitis. Typically administered via injection 30 minutes before therapy, patient studies have been promising, showing a reduced risk of developing radiation esophagitis. The goal when treating this condition is adequate nutrition intake, and it is advisable for patients to refrain from eating hot or spicy foods that can further irritate the esophageal lining. In severe cases, perforations, ulcerations, dysmotility, and tracheoesophageal fistulas can be seen. Although there is no cure for radiation esophagitis, symptoms regress 2 to 4 weeks after the completion of radiation treatment.
- Amifostine Analog, DRDE-30, Attenuates Bleomycin-Induced Pulmonary Fibrosis in Mice. [Journal Article]
- FPFront Pharmacol 2018; 9:394
- Bleomycin (BLM) is an effective curative option in the management of several malignancies including pleural effusions; but pulmonary toxicity, comprising of pneumonitis and fibrosis, poses challenge ...
Bleomycin (BLM) is an effective curative option in the management of several malignancies including pleural effusions; but pulmonary toxicity, comprising of pneumonitis and fibrosis, poses challenge in its use as a front-line chemotherapeutic. Although Amifostine has been found to protect lungs from the toxic effects of radiation and BLM, its application is limited due to associated toxicity and unfavorable route of administration. Therefore, there is a need for selective, potent, and safe anti-fibrotic drugs. The current study was undertaken to assess the protective effects of DRDE-30, an analog of Amifostine, on BLM-induced lung injury in C57BL/6 mice. Whole body micro- computed tomography (CT) was used to non-invasively observe tissue damage, while broncheo-alveolar lavage fluid (BALF) and lung tissues were assessed for oxidative damage, inflammation and fibrosis. Changes in the lung density revealed by micro-CT suggested protection against BLM-induced lung injury by DRDE-30, which correlated well with changes in lung morphology and histopathology. DRDE-30 significantly blunted BLM-induced oxidative stress, inflammation and fibrosis in the lungs evidenced by reduced oxidative damage, endothelial barrier dysfunction, Myeloperoxidase (MPO) activity, pro-inflammatory cytokine release and protection of tissue architecture, that could be linked to enhanced anti-oxidant defense system and suppression of redox-sensitive pro-inflammatory signaling cascades. DRDE-30 decreased the BLM-induced augmentation in BALF TGF-β and lung hydroxyproline levels, as well as reduced the expression of the mesenchymal marker α-smooth muscle actin (α-SMA), suggesting the suppression of epithelial to mesenchymal transition (EMT) as one of its anti-fibrotic effects. The results demonstrate that the Amifostine analog, DRDE-30, ameliorates the oxidative injury and lung fibrosis induced by BLM and strengthen its potential use as an adjuvant in alleviating the side effects of BLM.
- Corrigendum. [Journal Article]
- JDJ Dent Res 2018 May 01; :22034518774759
- Varghese JJ, Schmale IL, Mickelsen D, Hansen ME, Newlands SD, Benoit DSW, Korshunov VA, Ovitt CE. 2018. Localized delivery of amifostine enhances salivary gland radioprotection. J Dent Res [epub ahea...
Varghese JJ, Schmale IL, Mickelsen D, Hansen ME, Newlands SD, Benoit DSW, Korshunov VA, Ovitt CE. 2018. Localized delivery of amifostine enhances salivary gland radioprotection. J Dent Res [epub ahead of print 10 April 2018] in press. (Original DOI: 10.1177/0022034518767408) In the original online article, the third author's name was misspelled as D. Mickelson. This has been corrected to D. Mickelsen online and in print.
- A Review of Clinical Radioprotection and Chemoprotection for Oral Mucositis. [Review]
- TOTransl Oncol 2018 Apr 23; 11(3):771-778
- The first tenet of medicine, "primum non nocere" or "first, do no harm", is not always compatible with oncological interventions e.g., chemotherapy, targeted therapy and radiation, since they commonl...
The first tenet of medicine, "primum non nocere" or "first, do no harm", is not always compatible with oncological interventions e.g., chemotherapy, targeted therapy and radiation, since they commonly result in significant toxicities. One of the more frequent and serious treatment-induced toxicities is mucositis and particularly oral mucositis (OM) described as inflammation, atrophy and breakdown of the mucosa or lining of the oral cavity. The sequelae of oral mucositis (OM), which include pain, odynodysphagia, dysgeusia, decreased oral intake and systemic infection, frequently require treatment delays, interruptions and discontinuations that not only negatively impact quality of life but also tumor control and survivorship. One potential strategy to reduce or prevent the development of mucositis, for which no effective therapies exist only best supportive empirical care measures, is the administration of agents referred to as radioprotectors and/or chemoprotectors, which are intended to differentially protect normal but not malignant tissue from cytotoxicity. This limited-scope review briefly summarizes the incidence, pathogenesis, symptoms and impact on patients of OM as well as the background and mechanisms of four clinical stage radioprotectors/chemoprotectors, amifostine, palifermin, GC4419 and RRx-001, with the proven or theoretical potential to minimize the development of mucositis particularly in the treatment of head and neck cancers.
- Localized Delivery of Amifostine Enhances Salivary Gland Radioprotection. [Journal Article]
- JDJ Dent Res 2018 Apr 01; :22034518767408
- Radiotherapy for head and neck cancers commonly causes damage to salivary gland tissue, resulting in xerostomia (dry mouth) and numerous adverse medical and quality-of-life issues. Amifostine is the ...
Radiotherapy for head and neck cancers commonly causes damage to salivary gland tissue, resulting in xerostomia (dry mouth) and numerous adverse medical and quality-of-life issues. Amifostine is the only Food and Drug Administration-approved radioprotective drug used clinically to prevent xerostomia. However, systemic administration of amifostine is limited by severe side effects, including rapid decrease in blood pressure (hypotension), nausea, and a narrow therapeutic window. In this study, we demonstrate that retroductal delivery of amifostine and its active metabolite, WR-1065, to murine submandibular glands prior to a single radiation dose of 15 Gy maintained gland function and significantly increased acinar cell survival. Furthermore, in vivo stimulated saliva secretion was maintained in retrograde-treated groups at levels significantly higher than irradiated-only and systemically treated groups. In contrast to intravenous injections, retroductal delivery of WR-1065 or amifostine significantly attenuated hypotension. We conclude that localized delivery to salivary glands markedly improves radioprotection at the cellular level, as well as mitigates the adverse side effects associated with systemic administration. These results support the further development of a localized delivery system that would be compatible with the fractionated dose regimen used clinically.
- How to feed patients with gastrointestinal mucositis. [Journal Article]
- COCurr Opin Support Palliat Care 2018; 12(2):168-173
- CONCLUSIONS: Although options for prevention and treatment of chemotherapy or radiotherapy-induced gastrointestinal mucositis today are still limited, inadequate energy and nutrient intake should trigger nutritional interventions, including counselling, oral nutritional supplements, tube feeding and parenteral nutrition. To prevent gastrointestinal mucositis, several new agents have shown promising results in preclinical trials.
- Insufficient evidence for interventions to prevent dry mouth and salivary gland dysfunction post head and neck radiotherapy. [Journal Article]
- EBEvid Based Dent 2018 Mar 23; 19(1):30-31
- Data sourcesCochrane Oral Health's Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), Medline, Embase, CINAHL, EBSCO (Cumulative Index to Nursing and Allied Health Literat...
Data sourcesCochrane Oral Health's Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), Medline, Embase, CINAHL, EBSCO (Cumulative Index to Nursing and Allied Health Literature, LILACS, BIREME, Virtual Health Library (Latin American and Caribbean Health Science Information database), Zetoc Conference Proceedings, the US National Institutes of Health Ongoing Trials Register, (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry Platform for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases.Study selectionThe review included randomised controlled trials, irrespective of their language of publication or publication status. Participants could be outpatients or inpatients. The review included trials comparing any pharmacological agent regimen, prescribed prophylactically for salivary gland dysfunction prior to or during radiotherapy, with placebo, no intervention or an alternative pharmacological intervention. Comparisons of radiation techniques were excluded.Data extraction and synthesisStandard Cochrane methodological processes were followed.ResultsThirty-nine studies that randomised 3520 participants were included; the number of participants analysed varied by outcome and time point. The studies were ordered into 14 separate comparisons with meta-analysis only being possible in three of those. We found low quality evidence to show that amifostine, when compared to a placebo or no treatment control, might reduce the risk of moderate to severe xerostomia (grade 2 or higher on a 0 to 4 scale) at the end of radiotherapy (risk ratio (RR) 0.35, 95% confidence interval (CI) 0.19 to 0.67; P = 0.001, three studies, 119 participants), and up to three months after radiotherapy (RR 0.66, 95% CI 0.48 to 0.92; P = 0.01, five studies, 687 participants), but there is insufficient evidence that the effect is sustained up to 12 months after radiotherapy (RR 0.70, 95% CI 0.40 to 1.23; P = 0.21, seven studies, 682 participants). We found very low quality evidence that amifostine increased unstimulated salivary flow rate up to 12 months after radiotherapy, both in terms of mg of saliva per five minutes (mean difference (MD) 0.32, 95% CI 0.09 to 0.55; P = 0.006, one study, 27 participants), and incidence of producing greater than 0.1 g of saliva over five minutes (RR 1.45, 95%CI 1.13 to 1.86; P = 0.004, one study, 175 participants).However, there was insufficient evidence to show a difference when looking at stimulated salivary flow rates. There was insufficient (very low quality) evidence to show that amifostine compromised the effects of cancer treatment when looking at survival measures. There was some very low quality evidence of a small benefit for amifostine in terms of quality of life (ten-point scale) at 12 months after radiotherapy (MD 0.70, 95% CI 0.20 to 1.20; P = 0.006, one study, 180 participants), but insufficient evidence at the end of and up to three-month post radiotherapy. A further study showed no evidence of a difference at 6, 12, 18 and 24-month post radiotherapy.There was low quality evidence that amifostine is associated with increases in: vomiting (RR 4.90, 95% CI 2.87 to 8.38; P < 0.00001, five studies, 601 participants); hypotension (RR 9.20, 95% CI 2.84 to 29.83; P = 0.0002, three studies, 376 participants); nausea (RR 2.60, 95% CI 1.81 to 3.74; P < 0.00001, four studies, 556 participants); and allergic response (RR 7.51, 95% CI 1.40 to 40.39; P = 0.02, three studies, 524 participants).The authors founded insufficient evidence (that was of very low quality) to determine whether or not pilocarpine performed better or worse than a placebo or no treatment control for the outcomes: xerostomia, salivary flow rate, survival and quality of life. There was some low quality evidence that pilocarpine was associated with an increase in sweating (RR 2.98, 95% CI 1.43 to 6.22; P = 0.004, five studies, 389 participants).The authors found insufficient evidence to determine whether or not palifermin performed better or worse than placebo for: xerostomia (low quality); survival (moderate quality); and any adverse effects. There was also insufficient evidence to determine the effects of the following interventions: biperiden plus pilocarpine, Chinese medicines, bethanechol, artificial saliva, selenium, antiseptic mouthrinse, antimicrobial lozenge, polaprezinc, azulene rinse and Venalot Depot (coumarin plus troxerutin).ConclusionsThere is some low quality evidence to suggest that amifostine prevents the feeling of dry mouth in people receiving radiotherapy to the head and neck (with or without chemotherapy) in the short- (end of radiotherapy) to medium-term (three-month post radiotherapy). However, it is less clear whether or not this effect is sustained to 12-month post radiotherapy. The benefits of amifostine should be weighed against its high cost and side effects. There was insufficient evidence to show that any other intervention is beneficial.
- Novel Formulation Strategy to Improve the Feasibility of Amifostine Administration. [Journal Article]
- PRPharm Res 2018 Mar 19; 35(5):99
- CONCLUSIONS: Orally administered AMF achieves a similar systemic bioavailability and decreased peak plasma level of WR-1065 compared to intravenously administered AMF, suggesting oral AMF formulations maintain radioprotective efficacy without causing onerous side effects, and are clinically feasible.
- Protective effects of amifostine, curcumin and caffeic acid phenethyl ester against cisplatin-induced testis tissue damage in rats. [Journal Article]
- ETExp Ther Med 2018; 15(4):3404-3412
- Cisplatin is an effective antineoplastic drug that is usually used to treat a number of different types of cancer in the clinic. One of the most notable side effects of cisplatin use is infertility. ...
Cisplatin is an effective antineoplastic drug that is usually used to treat a number of different types of cancer in the clinic. One of the most notable side effects of cisplatin use is infertility. The present study was designed to determine the non-oxidative testicular effects caused by the use of cisplatin in rats. The rats were randomly allocated to the experimental groups. The untreated rats represented the control group (group I) and the treatment groups were as follows: cisplatin alone (group II), cisplatin+amifostine (group III), cisplatin+curcumin (group IV), and cisplatin+caffeic acid phenethyl ester (CAPE; group V). The present study observed that following cisplatin administration, the expression of nuclear factor-κB (NF-κβ)/p65, caspase-3 and 8-deoxyguanosine (8-OHdG) increased in germinal epithelium and Leydig cells. However, the expression of these markers decreased in groups III-V, most notably in the group treated with amifostine. cisplatin induced-damage was countered by amifostine and curcumin. The results revealed that the activation of NF-κB, caspase-3 and 8-OHdG had a significant role in cisplatin-induced testicular toxicity. Thus, amifostine, curcumin and, to a lesser extent, CAPE have the potential for use as therapeutic adjuvants in cisplatin-induced testis injury.
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- Cancer Incidence in C3H Mice Protected from Lethal Total-Body Radiation after Amifostine. [Journal Article]
- RRRadiat Res 2018; 189(5):490-496
- Amifostine is a potent antioxidant that protects against ionizing radiation effects. In this study, we evaluated the effect of Amifostine administered before total-body irradiation (TBI), at a drug d...
Amifostine is a potent antioxidant that protects against ionizing radiation effects. In this study, we evaluated the effect of Amifostine administered before total-body irradiation (TBI), at a drug dose that protects against TBI lethality, for potential protection against radiation-induced late effects such as a shortened lifespan and cancer. Three groups of mice were studied: 0 Gy control; 10.8 Gy TBI with Amifostine pretreatment; and 5.4 Gy TBI alone. Animals were monitored for their entire lifespan. The median survival times for mice receiving 0, 5.4 or 10.8 Gy TBI were 706, 460 and 491 days, respectively. Median survival of both irradiated groups was significantly shorter compared to nonirradiated mice ( P < 0.0001). Cancer incidence (hematopoietic and solid tumors) was similar between the irradiated groups and was significantly greater than for the 0 Gy controls. The ratio of hematopoietic-to-solid tumors differed among the groups, with the 5.4 Gy group having a higher incidence of hematopoietic neoplasms compared to the 10.8 Gy/Amifostine group (1.8-fold). Solid tumor incidence was greater in the 10.8 Gy/Amifostine group (1.6-fold). There are few mouse lifespan studies for agents that protect against radiation-induced lethality. Mice treated with 10.8 Gy/Amifostine yielded a lower incidence of hematopoietic neoplasms and higher incidence of solid neoplasms. In conclusion, mice protected from lethal TBI have a shortened lifespan, due in large part to cancer induction after exposure compared to nonexposed controls. Amifostine treatment did protect against radiation-induced hematopoietic tumors, while protection against solid neoplasms was significant but incomplete.