Insufficient evidence for interventions to prevent dry mouth and salivary gland dysfunction post head and neck radiotherapy

Abstract

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...

Medicinal Thiols: Current Status and New Perspectives

“…In a rat model of radiation-induced bone weakening, amifostine showed significant protection of bone mineral, but not of collagen [125], and in a study of RT-induced retinopathy in female rats, it was concluded that amifostine was more effective at preserving the inner and outer plexiform layers than the retina at 12 hours post-irradiation [126]. In humans, a metaanalysis suggested that amifostine was the only intervention that prevented moderate to severe xerostomia, salivary flow, and overall quality of life in RT patients [127]. Another study showed that amifostine significantly reduced the risk of grade 2 or higher esophageal toxicity and pulmonary toxicity.…”

“…Radioprotection [113,119,[121][122][123][124][125][126][127][128][129][130][131][132][133][134] Scavenges free radicals formed during RT -Captopril Hypertension [163,[165][166] Blocks activation of angiotensin, a vasoconstrictor Lead toxicity [89] Radioprotection [136][137][138][139] Metallo-β-lactamase inhibition [167][168][169] Alzheimer's/dementia [173,174] Dimercaprol, BAL in oil Heavy metal toxicity As, Au, Hg, and Pb [71][72][94][95][96] Chelates heavy metals, facilitating their removal -2,3-meso-Dimercaptosuccinic acid…”

Modelling Radiation-Induced Salivary Dysfunction during IMRT and Chemotherapy for Nasopharyngeal Cancer Patients

“…Due to the negative impact of late salivary dysfunction on HNC patients' QoL and the lack of an effective management strategy [14], a great deal of effort has been made in the last few decades to identify patient-and therapy-related factors and to build predictive models for late toxicity to determine treatment planning optimisation goals to possibly minimise the insurgence of such side effects, i.e., identify organs to be possibly spared and dose volume cutoffs to be utilised [15][16][17][18][19][20].…”

The efficacy and safety of amifostine for the acute radiation syndrome

“…An enhanced uptake by the salivary gland and kidneys may be responsible for privileged protection of these tissues and organs. A recent study suggested that amifostine does not have a significant effect for preventing xerostomia and the benefits of amifostine should be weighed against its high cost and side effects [41].…”