Parasympathomimetic drugs for the treatment of salivary gland dysfunction due to radiotherapy Stable (no update expected for reasons given in 'What's new')

Abstract

Abstract 

Background 

This is an updated version of the original Cochrane review on parasympathomimetic drugs for the treatment of salivary gland dysfunction due to radiotherapy (published in Issue 3, 2007). Salivary gland dysfunction is a predictable side effect of radiotherapy to the head and neck region. Pilocarpine hydrochloride (a choline ester) is licensed in many countries for the treatment of radiation‐induced salivary gland dysfunction. Other parasympathomimetics have also been used 'off licence' in the treatment of this condition.

Objectives 

To determine the efficacy and tolerability of parasympathomimetic drugs in the treatment of radiation‐induced salivary gland dysfunction (specifically radiation‐induced xerostomia).

Search methods 

For this update, we ran searches of the Cochrane Oral Health Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 6), MEDLINE, EMBASE, and CINAHL in July 2015. We checked the reference lists of retrieved articles for additional studies, contacted experts in the field for unpublished and ongoing trials, and contacted relevant pharmaceutical companies for unpublished and ongoing trials.

Selection criteria 

The selection criteria for the review were: 1) randomised controlled trials; 2) people suffering from radiation‐induced salivary gland dysfunction; 3) people treated with parasympathomimetic drugs; and 4) assessable data available on primary outcome measure.

Data collection and analysis 

The two review authors independently collected data from the full‐text version of relevant papers including: 1) citation details; 2) participants; 3) interventions; 4) assessments; 5) outcomes (that is efficacy, tolerability); and 6) quality issues.

Due to a lack of appropriate data, we were unable to perform a meta‐analysis.

Main results 

In the original review, three studies, including a total of 298 participants, fulfilled the inclusion criteria. All three studies involved the use of pilocarpine hydrochloride. We have included no additional studies in the update of the review; we have excluded eight additional studies.

The data suggest that pilocarpine hydrochloride is more effective than placebo and at least as effective as artificial saliva. The response rate was 42% to 51%. The time to response was up to 12 weeks. The overall side effect rate was high, and side effects were the main reason for withdrawal (6% to 15% of participants taking 5 mg three times a day had to withdraw). The side effects were usually the result of generalised parasympathomimetic stimulation (for example sweating, headaches, urinary frequency, vasodilatation). Response rates were not dose dependent, but side effect rates were dose dependent.

Authors' conclusions 

There is limited evidence to support the use of pilocarpine hydrochloride in the treatment of radiation‐induced xerostomia. Currently, there is little evidence to support the use of other parasympathomimetic drugs in the treatment of radiation‐induced xerostomia. Available studies suggest that approximately half of patients will respond, but side effects can be problematic. The conclusions of the update are the same as the conclusions of the original review, since no new relevant studies have been published in the interim.

Author(s)

Andrew N Davies, Jo Thompson

Abstract

Plain language summary 

Parasympathomimetic drugs for the treatment of 'dry mouth' due to radiotherapy 

This updated review found there is limited evidence to support the use of pilocarpine hydrochloride in the treatment of radiation‐induced salivary gland dysfunction ('dry mouth'). Salivary gland damage is a frequent and important complication of radiotherapy to the head and neck area; it causes dryness of the mouth with resultant problems with eating, talking, and local infection. The parasympathomimetic group of drugs have been used to treat radiotherapy‐induced salivary gland damage.

We identified three studies that involved a total of 289 participants, and they all used the drug pilocarpine.

The review found that 42% to 51% of participants (4 to 5 in 10) responded to pilocarpine, although in some participants the response did not occur for up to 12 weeks. Pilocarpine was more effective than a placebo treatment, and at least as effective as an artificial saliva.

Side effects were common with pilocarpine (for example sweating, headache, passing urine frequently, flushing), but were usually reported to be mild; 6% to 15% (0.6 to 1.5 in 10) participants had to stop taking pilocarpine due to side effects.

The findings of this review are limited by the small number of good‐quality trials that have been performed in this area. The update of this review did not find any new information on this topic.

Author(s)

Andrew N Davies, Jo Thompson

Reviewer's Conclusions

Authors' conclusions 

Implications for practice 

The conclusions of the updated review are the same as the conclusions of the original review, in spite of the publication of additional RCTs.

For people with radiation‐induced salivary gland dysfunction: 

There is limited evidence to support the use of pilocarpine hydrochloride in the treatment of radiation‐induced xerostomia. It would seem appropriate to offer patients a trial of the drug, assuming that there are no contraindications (that is uncontrolled asthma, uncontrolled chronic obstructive pulmonary disease, uncontrolled cardiorenal disease, acute iritis, pregnancy, breast‐feeding) to the use of the drug.

For clinicians: 

It would seem appropriate to offer patients a trial of the drug. The trial should be prolonged, since the response can be delayed (up to 12 weeks). The dose used should be 5 mg three times a day to keep side effects to a minimum, since the adverse effects are dose dependent (and the response does not appear to be dose dependent). However, many patients fail to respond to pilocarpine hydrochloride. Currently, there is little evidence to support the use of other parasympathomimetic drugs in the treatment of radiation‐induced xerostomia.

For policymakers and funders: 

A trial of pilocarpine is recommended for people with symptomatic radiation‐induced salivary gland dysfunction, and policymakers/funders should support this option for treatment.

Implications for research 

Additional studies are required to clarify the role of other parasympathomimetic drugs in the treatment of radiation‐induced xerostomia. Similarly, additional studies are also required to clarify the role of other interventions in the treatment of radiation‐induced xerostomia (for example saliva substitutes, other saliva stimulants). The aim of such studies should be to determine whether these other interventions have greater efficacy or tolerability, or both, as compared to pilocarpine. It is important that future studies focus on the impact of these interventions on the symptoms of salivary gland dysfunction (for example xerostomia, oral discomfort), since these are the 'outcome measures' that determine adherence or non‐adherence with treatment. It is equally important that future studies assess the impact of these interventions on the important complications of salivary gland dysfunction (for example dental caries, oral candidosis).

In addition, studies are required in people who have undergone intensity‐modulated radiotherapy (and other tissue‐sparing techniques) as well as in people who have undergone so‐called conventional radiotherapy.

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