NIHR DC Discover

NIHR Signal Pilocarpine improves dry mouth caused by radiotherapy

Published on 7 November 2017

doi: 10.3310/signal-000499

Out of several treatments tested, the drug pilocarpine gave the most significant improvement in dry mouth following radiotherapy for head and neck cancer. Less dry mouth and increased salivary flow were twice as likely after taking pilocarpine than after a dummy pill.

Dry mouth from radiotherapy impairs quality of life. Although people can try simple measures at home, such as sucking ice cubes, they may wish to discuss pilocarpine treatment with their GP. Side effects from this medication are usually short-lived but if they are troublesome other options are available, though not supported by such good evidence as pilocarpine.

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Why was this study needed?

Every day in the UK, 31 people are diagnosed with a type of head and neck cancer. Radiotherapy, a common treatment, often causes dry mouth. This can lead to mouth discomfort, a change in taste, dental disease and problems speaking, chewing and swallowing.

Several treatments are available. Chewing gum and sucking sweets or ice are thought to stimulate saliva production. Artificial saliva can be given as a lozenge, spray or gel. Drugs, such as pilocarpine, have been available to stimulate saliva production for many years but can cause side effects including sweating, blurred vision and nausea.

This review aimed to systematically compare all available treatments for a dry mouth and reduced salivation after radiotherapy for head and neck cancer.

What did this study do?

This systematic review included 20 randomised controlled trials, three from the UK. Trials compared treatments with each other or a placebo among 1,732 adults with a dry mouth after radiotherapy. Interventions replaced or aimed to stimulate saliva production. They included mouth gels, toothpaste, acupuncture, laser therapy, herbal compounds, artificial saliva and two drugs – pilocarpine and cevimeline.

The trials of drugs were of high quality so we can be confident in these results. However, the trials of non-drug treatments had a high risk of certain bias because the person and assessor knew which treatment they were having. They were also mostly small trials of between 20 and 38 participants, so conclusions from these should be treated with caution.

What did it find?

  • People taking a pilocarpine tablet were twice as likely to have an improvement in sensation of a dry mouth. Defined as 25mm or more on a visual analogue scale from 0 to 100mm. This level of improvement was reported by 63/140 people (45%) on pilocarpine compared to 36/140 people (26%) on placebo, (odds ratio [OR] 2.37, 95% confidence interval [CI] 1.43 to 3.94, two trials).
  • There was also an improvement in salivary flow 60 minutes after taking oral pilocarpine for 89/129 people (69%) compared to 65/132 people (49%) on placebo, (OR 2.27, 95% CI 1.37 to 3.76, two trials).
  • Acupuncture did not increase salivary flow rate (mean difference 0.00, 95% CI ‑0.02 to 0.03). However, these trials were small with a total of 50 participants.
  • There was insufficient evidence on the effect of biotene gel, toothpaste, mouthcare systems, herbal medicine, humidifiers or laser therapy.

What does current guidance say on this issue?

Guidelines from the British Association of Head and Neck Oncologists (2016) state that pilocarpine may be offered as one option to improve radiation-induced dry mouth following radiotherapy to people with evidence of some intact salivary function. The recommended dose is 5 to 10mg per day.

What are the implications?

In recent years radiotherapy has been better targeted, and lower doses have been used, however, dry mouth is still an unpleasant and common side effect of treatment to the head and neck.

Pilocarpine remains an option in the treatment for persistent dry mouth after radiotherapy.

Though there was no robust evidence of the effectiveness of the other interventions, this does not mean that they aren’t useful. Given the limited number trial on these options, it is possible that they may still be worth trying. Some simple measures, like sucking ice or using saliva substitutes might be more appropriate for milder symptoms.

Citation and Funding

Mercadante V, Al Hamad A, Lodi G, et al. Interventions for the management of radiotherapy-induced xerostomia and hyposalivation: A systematic review and meta-analysis. Oral Oncol. 2017;66:64-74.

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Bibliography

British Association for Head and Neck Oncologists. Head and neck cancer: United Kingdom national multidisciplinary guidelines. Journal of Laryngology and Otology. 2016;(130):S2.

Cancer Research UK. Oral cancer incidence statistics. London; Cancer Research UK; accessed October 2017.

Cancer Research UK. Treating mouth problems. London; Cancer Research UK; 2015.

NICE. Cancer of the upper aerodigestive tract: assessment and management in people aged 16 and over. CG36. London: National Institute for Health and Care Excellence; 2016.

NICE. Improving outcomes in head and neck cancers.  London: National Institute for Clinical Excellence; 2004, reviewed 2015.

Patient. Dry mouth (Xerostomia). Patient Platform Ltd: London; 2015.

Riley P, Glenny AM, Hua F, Worthington HV. Pharmacological interventions for preventing dry mouth and salivary gland dysfunction following radiotherapy. Cochrane Database Syst Rev. 2017;(7):CD012744.

Why was this study needed?

Every day in the UK, 31 people are diagnosed with a type of head and neck cancer. Radiotherapy, a common treatment, often causes dry mouth. This can lead to mouth discomfort, a change in taste, dental disease and problems speaking, chewing and swallowing.

Several treatments are available. Chewing gum and sucking sweets or ice are thought to stimulate saliva production. Artificial saliva can be given as a lozenge, spray or gel. Drugs, such as pilocarpine, have been available to stimulate saliva production for many years but can cause side effects including sweating, blurred vision and nausea.

This review aimed to systematically compare all available treatments for a dry mouth and reduced salivation after radiotherapy for head and neck cancer.

What did this study do?

This systematic review included 20 randomised controlled trials, three from the UK. Trials compared treatments with each other or a placebo among 1,732 adults with a dry mouth after radiotherapy. Interventions replaced or aimed to stimulate saliva production. They included mouth gels, toothpaste, acupuncture, laser therapy, herbal compounds, artificial saliva and two drugs – pilocarpine and cevimeline.

The trials of drugs were of high quality so we can be confident in these results. However, the trials of non-drug treatments had a high risk of certain bias because the person and assessor knew which treatment they were having. They were also mostly small trials of between 20 and 38 participants, so conclusions from these should be treated with caution.

What did it find?

  • People taking a pilocarpine tablet were twice as likely to have an improvement in sensation of a dry mouth. Defined as 25mm or more on a visual analogue scale from 0 to 100mm. This level of improvement was reported by 63/140 people (45%) on pilocarpine compared to 36/140 people (26%) on placebo, (odds ratio [OR] 2.37, 95% confidence interval [CI] 1.43 to 3.94, two trials).
  • There was also an improvement in salivary flow 60 minutes after taking oral pilocarpine for 89/129 people (69%) compared to 65/132 people (49%) on placebo, (OR 2.27, 95% CI 1.37 to 3.76, two trials).
  • Acupuncture did not increase salivary flow rate (mean difference 0.00, 95% CI ‑0.02 to 0.03). However, these trials were small with a total of 50 participants.
  • There was insufficient evidence on the effect of biotene gel, toothpaste, mouthcare systems, herbal medicine, humidifiers or laser therapy.

What does current guidance say on this issue?

Guidelines from the British Association of Head and Neck Oncologists (2016) state that pilocarpine may be offered as one option to improve radiation-induced dry mouth following radiotherapy to people with evidence of some intact salivary function. The recommended dose is 5 to 10mg per day.

What are the implications?

In recent years radiotherapy has been better targeted, and lower doses have been used, however, dry mouth is still an unpleasant and common side effect of treatment to the head and neck.

Pilocarpine remains an option in the treatment for persistent dry mouth after radiotherapy.

Though there was no robust evidence of the effectiveness of the other interventions, this does not mean that they aren’t useful. Given the limited number trial on these options, it is possible that they may still be worth trying. Some simple measures, like sucking ice or using saliva substitutes might be more appropriate for milder symptoms.

Citation and Funding

Mercadante V, Al Hamad A, Lodi G, et al. Interventions for the management of radiotherapy-induced xerostomia and hyposalivation: A systematic review and meta-analysis. Oral Oncol. 2017;66:64-74.

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Bibliography

British Association for Head and Neck Oncologists. Head and neck cancer: United Kingdom national multidisciplinary guidelines. Journal of Laryngology and Otology. 2016;(130):S2.

Cancer Research UK. Oral cancer incidence statistics. London; Cancer Research UK; accessed October 2017.

Cancer Research UK. Treating mouth problems. London; Cancer Research UK; 2015.

NICE. Cancer of the upper aerodigestive tract: assessment and management in people aged 16 and over. CG36. London: National Institute for Health and Care Excellence; 2016.

NICE. Improving outcomes in head and neck cancers.  London: National Institute for Clinical Excellence; 2004, reviewed 2015.

Patient. Dry mouth (Xerostomia). Patient Platform Ltd: London; 2015.

Riley P, Glenny AM, Hua F, Worthington HV. Pharmacological interventions for preventing dry mouth and salivary gland dysfunction following radiotherapy. Cochrane Database Syst Rev. 2017;(7):CD012744.

Interventions for the management of radiotherapy-induced xerostomia and hyposalivation: A systematic review and meta-analysis.

Published on 19 January 2017

Mercadante V, Al Hamad A, Lodi G, Fedele S

Oral oncology Volume 66 , 2017

Salivary gland hypofunction is a common and permanent adverse effect of radiotherapy to the head and neck. Randomised trials of available treatment modalities have produced unclear results and offer little reliable guidance for clinicians to inform evidence-based therapy. We have undertaken this systematic review and meta-analysis to estimate the effectiveness of available interventions for radiotherapy-induced xerostomia and hyposalivation.We searched MEDLINE, Cochrane Central, EMBASE, AMED, and CINAHL database through July 2016 for randomised controlled trials comparing any topical or systemic intervention to active and/or non-active controls for the treatment of radiotherapy-induced xerostomia. The results of clinically and statistically homogenous studies were pooled and meta-analyzed.1732 patients from twenty studies were included in the systematic review. Interventions included systemic or topical pilocarpine, systemic cevimeline, saliva substitutes/mouthcare systems, hyperthermic humidification, acupuncture, acupuncture-like transcutaneous electrical nerve stimulation, low-level laser therapy and herbal medicine. Results from the meta-analysis, which included six studies, suggest that both cevimeline and pilocarpine can reduce xerostomia symptoms and increase salivary flow compared to placebo, although some aspects of the relevant effect size, duration of the benefit, and clinical meaningfulness remain unclear. With regard to interventions not included in the meta-analysis, we found no evidence, or very weak evidence, that they can reduce xerostomia symptoms or increase salivary flow in this population.Pilocarpine and cevimeline should represent the first line of therapy in head and neck cancer survivors with radiotherapy-induced xerostomia and hyposalivation. The use of other treatment modalities cannot be supported on the basis of current evidence.

A Visual Analogue Scale (VAS) is a tool used to help rate the intensity of subjective symptoms. In this case, one end of a straight line means no improvement in symptoms, and the other end (100mm) is the most improvement in symptoms.

Expert commentary

Curative radiation for head and neck cancer can leave patients with a dry mouth that significantly affects their quality of life.

Studying this requires attention to the patient’s symptoms (subjective measures) and preferably an understanding of saliva output (objective measures). The studies in this meta-analysis have chosen multiple ways to do both, none of them used consistently.

Medication appears to have a limited effect but with side effects and persistent questions about dose and duration.

Widespread focus on reducing dry mouth incidence should not detract from an acute need for better treatments.

Dr Richard Simcock, Consultant Clinical Oncologist, Sussex Cancer Centre, Brighton