Amifostine may relieve symptoms of salivary gland dysfunction in head and neck cancer patients


Problems with saliva production and salivary glands are a significant and mostly permanent side effect for people after radiotherapy treatment to the head and neck. When this occurs the condition is known as dry mouth or xerostomia. Dry mouth is not measurable and is a subjective or personal expression of how the mouth feels. It can have other causes and is a consequence of the production of less saliva or by the consistency of saliva. The rate of flow of saliva in an individual’s mouth however can be measured. People who have dry mouth have a reduced quality of life. They can experience issues with taste and general discomfort, difficulties chewing, swallowing and speaking as well as tooth decay, thrush and other infections of the mouth. A wide range of drugs that work in different ways have been used to try and prevent problems with salivary glands caused by radiotherapy. Unfortunately there is currently not enough evidence to show which drugs or which type of drugs are most effective.

What was the research?

A systematic review of the evidence to assess the effects of treatment with drugs in order to prevent damage to salivary glands following radiotherapy to the head and neck

Who conducted the research?

The research was conducted by a team led by Phil Riley from Cochrane Oral Health, based at the University of Manchester. Anne-Marie Glenny, Fang Hua and Helen V. Worthington were also on the team.

What evidence was included in the review?

The evidence in this review is current up to 14 September 2016. 39 randomised controlled trials were included with a total of 3520 participants. Participants were male and female, all ages and ethnic origins, out patients or in patients, who were scheduled to have radiation therapy with or without chemotherapy to the head and neck. Drugs included were any prescribed to prevent salivary gland problems and given before or during radiotherapy. Information was collected from the end of radiotherapy except for that about adverse effects. Different techniques for giving radiation treatment that might reduce damage were not included.The main outcomes measured were participant’s own assessment of dry mouth and the measurement of salivary flow. Secondary outcomes measured included adverse or unwanted effects such as sweating, crying, watery discharge from the nose, diarrhoea and nausea.

What did the evidence say?

There is some low-quality evidence to suggest that the drug 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 months after radiotherapy). However it is less clear whether or not this effect is sustained to 12 months after radiotherapy. The benefits of amifostine should be weighed against its high costs and side effects. Adverse effects of vomiting, low blood pressure, feeling of sickness and allergic response were all more frequent in those receiving amifostine. There was insufficient evidence to show that any other treatment is beneficial.

How good was the evidence?

The quality of evidence for amifostine was found to be low because of risk of bias, inconsistency and imprecision caused by the small number of studies in the comparison or sample size. A standardized scale for measuring participant’s experience of dry mouth would in future allow comparison and pooling together of results.

What are the implications for doctors, dentists and the general public?

Physicians should weigh up the benefits of amifostine against its high cost and side effects.

What should researchers look at in the future?

Further well conducted, well reported and adequately powered randomised controlled trials are needed to add to the evidence base for the interventions assessed in the single-study comparisons of this systematic review. Amifostine should be assessed with longer term follow-up to establish whether the promising shorter term effects are sustained. Palifermin should also be studied further and with longer follow-up. Trialists should endeavour to measure xerostomia consistently.


Riley P, Glenny AM, Hua F, Worthington HV. Pharmacological interventions for preventing dry mouth and salivary gland dysfunction following radiotherapy. Cochrane Database of Systematic Reviews 2017, Issue 7. Art. No.: CD012744. DOI: 10.1002/14651858.CD012744.

This post is an extended version of the review’s plain language summary, compiled by Anne Littlewood at the Cochrane Oral Health Group Editorial Base.