Review article

Salivary gland dysfunction (dry mouth) in patients with

cancer: a consensus statement
ecc_1081

172..177

A. DAVIES, frcp, consultant, Palliative Medicine, Royal Marsden Hospital, Sutton, Surrey, J. BAGG, phd,
professor, Clinical Microbiology, Glasgow Dental School, Glasgow, D. LAVERTY, msc, nurse consultant,
Palliative Care, St Josephs Hospice, London, P. SWEENEY, phd, clinical senior lecturer, Special Care Dentistry,
Glasgow Dental School, Glasgow, UK, M. FILBET, md, director, Palliative Care Unit, University Hospital Lyon
Sud, Lyon, France, K. NEWBOLD, md, consultant clinical oncologist, Royal Marsden Hospital, Sutton, UK, J.
DE ANDRS, md, associate professor, Anesthesiology, General University Hospital, Valencia, Spain, & S.
MERCADANTE, md, director, the Anaesthesia and Intensive Care and Pain Relief and Palliative Care Units,
University of Palermo La Maddalena Cancer Centre, Palermo, Italy
DAVIES A., BAGG J., LAVERTY D., SWEENEY P., FILBET M., NEWBOLD K., DE ANDRS J. &
MERCADANTE S. (2010) European Journal of Cancer Care 19, 172177
Salivary gland dysfunction (dry mouth) in patients with cancer: a consensus statement
A group of interested professionals was convened to develop some evidence-based recommendations on the
management of salivary gland dysfunction (SGD) in oncology patients. A Medline search was performed to
identify the literature on SGD. The abstracts of all identified papers were read, and the full texts of all relevant
papers were reviewed. The evidence was graded according to the Scottish Intercollegiate Guidelines Network
grading system for recommendations in evidence-based guidelines. The summary of the main recommendations are: (1) patients with cancer should be regularly assessed for SGD (grade of recommendation D); (2) the
management of SGD should be individualised (D); (3) consideration should be given to strategies to prevent the
development of radiation-induced SGD (C); (4) consideration should be given to treatment of the cause(s) of the
SGD (C); (5) the treatment of choice for the symptomatic management of SGD is use of an appropriate saliva
stimulant (C); (6) consideration should be given to prevention of the complications of the SGD (D); (7)
consideration should be given to treatment of the complications of the SGD (D); and (8) patients with SGD
should be regularly reassessed (D).

Keywords: salivary gland dysfunction, xerostomia, salivary gland hypofunction, neoplasms.

IN TR O D U C T I O N
Xerostomia has been defined as the subjective sensation
of dryness of the mouth (Sreebny 1996), while salivary
gland hypofunction has been defined as any objectively
demonstrable reduction in either whole and/or individual

Correspondence address: Andrew Davies, Consultant in Palliative Medicine, Royal Marsden Hospital, Downs Road, Sutton, Surrey SM2 5PT, UK
(e-mail: andrew.davies@rmh.nhs.uk).

Accepted 13 October 2008

DOI: 10.1111/j.1365-2354.2009.01081.x
European Journal of Cancer Care, 2010, 19, 172177

2009 The Authors

Journal compilation 2009 Blackwell Publishing Ltd

gland flow rates (Navazesh et al. 1992). Xerostomia is

usually the result of a decrease in the volume of saliva
secreted (i.e. salivary gland hypofunction). However,
xerostomia may also result from a change in the composition of the saliva secreted (Pankhurst et al. 1996a). Salivary gland dysfunction (SGD) is an umbrella term to
describe patients with xerostomia and/or salivary gland
hypofunction (Davies 2005a), and this term will be preferentially used throughout this document.
The prevalence of xerostomia is 2226% in the general
population (Billings et al. 1996; Nederfors et al. 1997),
whereas the prevalence of xerostomia has been reported to
be 5455% in mixed oncology populations (Portenoy et al.

SGD in patients with cancer

Table 1. Causes of cancer-related salivary gland dysfunction

Cancer-related
Tumour infiltration*
Paraneoplastic syndrome* (Folli et al. 1997)
Cancer treatment-related
Surgery* (Schubert & Izutsu 1987)
Radiotherapy (Jensen et al. 2003)
Radionuclide therapy (e.g. I131 therapy) (Solans et al. 2001)
Chemotherapy (Jensen et al. 2003)
Biological therapy (e.g. interleukin-2) (Nagler et al. 2001)
Graft-versus-host disease (Nagler et al. 1996)
Other causes
Drug treatment (Davies et al. 2001)
Dehydration
Malnutrition
Decreased oral intake (e.g. PEG feeding)
Decreased mastication (e.g. liquid diet)
Anxiety
Depression
Sjgrens syndrome
Other disorders of salivary glands
Neurological disorders

*Uncommon causes.

Most common cause.

1994; Chang et al. 2000) and to be 7882% in advanced

oncology populations (Davies et al. 2001; Tranmer et al.
2003). Indeed, xerostomia is one of the most common
symptoms experienced by all groups of oncology patients.
The prevalence of salivary gland hypofunction has been
reported to be 8283% in advanced oncology populations
(Chaushu et al. 2000; Davies et al. 2002).
The aetiology of SGD in oncology patients is very variable (Table 1) (Schubert & Izutsu 1987; Nagler et al.
1996, 2001; Folli et al. 1997; Davies et al. 2001; Solans
et al. 2001; Jensen et al. 2003). However, the most
common cause in this group of patients is drug treatment. SGD is a common side effect of many types of
drug, including many supportive care drugs (e.g. analgesics, anti-emetics) (Sreebny & Schwartz 1997). The clinical features of SGD in oncology patients are also very
variable (Table 2) (Sreebny & Valdini 1988; Korsten et al.
1991; Bckstrm et al. 1995; Pankhurst et al. 1996b;
Davies et al. 2001; Leone & Oppenheim 2001; Rydholm
& Strang 2002; Davies & Vriens 2005; Dirix et al. 2008).
SGD is associated with a variety of oral problems, but is
also associated with more generalised problems. Indeed,
SGD is associated with a significant negative impact on
quality of life in this group of patients (Rydholm &
Strang 2002).
In spite of the aforementioned facts, SGD remains an
orphan topic within oncology and supportive care
(Senn 1997). SGD is consistently under-diagnosed within
oncology populations. It is well recognised that patients
with head and neck cancer are prone to SGD, but not
2009 The Authors
Journal compilation 2009 Blackwell Publishing Ltd

that other groups of cancer patients are also at risk of

this problem. Moreover, SGD is consistently undertreated/mistreated within oncology populations. Thus,
a consensus group of interested healthcare professionals was convened to develop evidence-based recommendations on the management of SGD in oncology
patients.

ME THODOL OGY
The consensus group was multidisciplinary in nature,
with representatives from the fields of oncology, palliative
care and dentistry. An initial face-to-face meeting was
arranged to determine the scope of the consensus group
and to produce an outline of the consensus statement. A
first draft of the document was developed, circulated to
the group for comments/amendments, and then the final
draft of the document was produced.
A Medline search was performed to identify the literature on SGD. The search terms used were xerostomia,
salivary gland hypofunction and salivary gland dysfunction, the database searched was 1950 to July 2007, and the
search limits used were human and English language.
Additional papers were identified from the reference lists
of reviewed papers, the reference lists of relevant textbooks and the reviewers personal files. The abstracts of
all identified papers were read, and the full texts of all
relevant papers were reviewed.
The evidence was graded according to the Scottish Intercollegiate Guidelines Network grading system for recommendations in evidence-based guidelines (Harbour &
Miller 2001). In many cases the recommendations relate
to a range of different interventions, and in some cases the
level of evidence was different for the individual interventions. In the latter instance, the recommendation was
graded according to what was considered to be the overall
level of evidence.

RE C OMME NDA TI ONS

The group feels unable to make recommendations about
any individual treatment options, but does feel able to
make recommendations about certain generic management strategies (Table 3):

Patients with cancer should be regularly assessed for

salivary gland dysfunction (grade of
recommendation D)
Studies suggest that there is a disparity between the presence of SGD and the reporting of SGD (Shorthose &
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DAVIES et al.

Table 2. Complications of salivary gland dysfunction

General problems

Oral discomfort (Davies et al. 2001)

Fissuring of oral mucosa
Lip discomfort (Sreebny & Valdini 1988)
Cracking of lips

Eating-related problems

Anorexia (Davies et al. 2001)

Taste disturbance (Davies et al. 2001)
Difficulty chewing (Davies et al. 2001)
Difficulty swallowing (Davies et al. 2001)
Decreased intake of nutrition (Bckstrm et al. 1995)

Speaking-related problems

Difficulty speaking (Davies et al. 2001)

Oral hygiene

Poor oral hygiene

Halitosis

Oral infections

Oral candidosis (Davies et al. 2006)

Dental caries (Leone and Oppenheim 2001)
Periodontal disease
Staphylococcal mucositis
Salivary gland infections

Systemic infections

Secondary to oral infection (e.g. pneumonia, septicaemia)

Dental/denture problems

Dental erosion (leading to dental sensitivity/trauma to the oral mucosa)

Poorly fitting dentures (leading to trauma to the oral mucosa) (Pankhurst et al. 1996b)

Psychosocial problems

Embarrassment (Rydholm & Strang 2002)

Anxiety (Rydholm & Strang 2002)
Depression (Dirix et al. 2008)
Social isolation (Rydholm & Strang 2002)

Miscellaneous problems

Difficulty swallowing oral medication

Difficulty using oral transmucosal medication (i.e. sublingual/buccal medication) (Davies & Vriens 2005)
Sleep disturbance (Rydholm & Strang 2002)
Oesophagitis (Korsten et al. 1991)
Urinary frequency (secondary to increased intake of fluid)

Table 3. Consensus panel recommendations

Patients with cancer should be regularly assessed for salivary gland dysfunction (grade of recommendation D)
The management of salivary gland dysfunction should be individualised (grade of recommendation D)
Consideration should be given to strategies to prevent the development of radiation-induced salivary gland dysfunction (grade of
recommendation C)
Consideration should be given to treatment of the cause(s) of the salivary gland dysfunction (grade of recommendation C)
The treatment of choice for the symptomatic management of salivary gland dysfunction is use of an appropriate saliva stimulant
(grade of recommendation C)
Consideration should be given to prevention of the complications of the salivary gland dysfunction (grade of recommendation D)
Consideration should be given to treatment of the complications of the salivary gland dysfunction (grade of recommendation D)
Patients with salivary gland dysfunction should be regularly reassessed (grade of recommendation D)
More education is required about the problem of cancer-related salivary gland dysfunction (grade of recommendation D)
More research is required into the problem of cancer-related salivary gland dysfunction (grade of recommendation D)

Andrew 2003). Thus, all patients with cancer should be

formally assessed for SGD. All patients should be asked
about the presence of xerostomia, and patients with
xerostomia should be asked about the presence of other
relevant symptoms (and examined for the presence of relevant complications) (Davies 2005b). The initial assessment can be performed by any/all members of the
multidisciplinary team (MDT), while the latter assessment should be performed by healthcare professionals
with training in oral problems.
174

The management of salivary gland dysfunction should

be individualised (grade of recommendation D)
Salivary gland dysfunction is a heterogeneous condition,
and so requires individualised management. The optimal
management of SGD depends on a variety of interrelated
factors, including the aetiology of the SGD, the clinical
features of the SGD, the presence of teeth, the availability
of interventions, the general condition of the patient and
(most importantly) the preferences of the patient.
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Journal compilation 2009 Blackwell Publishing Ltd

SGD in patients with cancer

The management of SGD is often multidimensional and

may involve both dental members of the MDT (e.g.
dentist, dental hygienist) and non-dental members of the
MDT (e.g. doctors, nurses). It is important that a treatment plan is developed, and that someone within the
MDT takes responsibility for ensuring that the treatment
plan is followed.

Consideration should be given to strategies to prevent

the development of radiation-induced salivary gland
dysfunction (grade of recommendation C)
A number of strategies have been reported to prevent/
ameliorate radiation-induced SGD, including surgical
relocation of the salivary glands (Jha et al. 2003), use of
specific radiotherapy techniques (e.g. intensity-modulated
radiation therapy) (Amosson et al. 2002) and the use of
radioprotectors (e.g. amifostine) (Sasse et al. 2006). At
present, the use of specific radiotherapy techniques is the
only strategy that has been widely adopted within the
European Union.

Consideration should be given to treatment of the

cause(s) of the salivary gland dysfunction (grade of
recommendation C)
The main causes of SGD are shown in Table 1. Some of
these causes are amenable to specific interventions,
although most are not amenable to specific interventions.
The most common cause of SGD is drug treatment. In
theory it is possible to discontinue or substitute the relevant drugs. However, in practice it is usually difficult to
discontinue many of these drugs, because they are necessary for symptom control. Similarly, it is usually futile to
substitute many of these drugs because the problem is a
drug class side effect (rather than an individual drug side
effect).

The treatment of choice for the symptomatic

management of salivary gland dysfunction is use of an
appropriate saliva stimulant (grade of
recommendation C)
The symptomatic management of SGD involves the use
of saliva stimulants (agents that promote saliva secretion) and saliva substitutes (agents that replace missing
saliva). As discussed above, the choice of symptomatic
treatment will depend on a variety of interrelated
factors.
2009 The Authors
Journal compilation 2009 Blackwell Publishing Ltd

There are good theoretical reasons for prescribing

saliva stimulants rather than saliva substitutes (Davies
2005a). The saliva stimulants cause an increase in secretion of normal saliva, and so will ameliorate the
xerostomia and the other complications of SGD. In
contrast, the saliva substitutes (which are physically/
biochemically very different from normal saliva) will
generally ameliorate only the xerostomia. Furthermore,
in the studies that have compared saliva stimulants
with saliva substitutes, patients have generally preferred the saliva stimulants (Bjrnstrm et al. 1990).
Nevertheless, some patients do not respond to saliva
stimulants (e.g. some patients with radiation-induced
SGD).
A number of different saliva stimulants have been
used in clinical practice, including sugar-free chewing
gum, sugar-free sweets, organic acids (e.g. ascorbic
acid, citric acid), parasympathomimetic drugs (e.g.
pilocarpine hydrochloride, bethanechol chloride), other
drugs (e.g. anetholtrithione and yohimbine) and various
non-pharmacological methods (e.g. acupuncture, electrostimulation) (Davies 2005a). As discussed above, the
choice of a specific stimulant depends on a number of
interrelated factors. However, use of the organic
acids should be avoided in dentate patients and probably avoided in all patients. (Acidic products will
contribute to complications such as mucosal irritation, dental erosion, dental caries and oral
candidosis).
Pilocarpine hydrochloride should be considered to be
the saliva stimulant of choice in the management of
radiation-induced SGD. However, the response rate is
only 4251%, and the time to response is up to 12 weeks
(Davies & Shorthose 2007). Furthermore, the side effect
rate is relatively high, and side effects are the main reason
for withdrawal from studies (Davies & Shorthose 2007).
The side effects are usually the result of generalised parasympathomimetic stimulation (e.g. sweating, headaches,
urinary frequency, vasodilatation).
A number of different saliva substitutes have been used
in clinical practice, including water, artificial saliva and
various everyday compounds (e.g. butter and vegetable oil)
(Davies 2005a). Artificial saliva products are a diverse
group of substances and differ in terms of the formulation
(e.g. spray, gel), the lubricant (e.g. mucin, carboxymethylcellulose) and other ingredients (e.g. fluoride, antibacterial
agents). Again, as discussed above, the choice of a specific
substitute depends on a number of interrelated factors.
However, the use of acidic artificial saliva products should
be avoided in dentate patients and probably avoided in all
patients.
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DAVIES et al.

Consideration should be given to prevention of the

complications of the salivary gland dysfunction (grade of
recommendation D)

difficult-to-manage SGD should be referred in a timely

manner to a specialist with an interest in SGD.

The main complications of SGD are shown in Table 2.

Adequate management of SGD may prevent the development of these complications. Nevertheless, certain preventative strategies should be considered in all patients
with SGD:

More education is required about the problem of

cancer-related salivary gland dysfunction (grade of
recommendation D)

1 Maintenance of oral hygiene dentate patients need to

clean their teeth at least twice a day, and edentulous
patients need to clean their dentures at least once a day
and to remove their dentures at night-time (Sweeney
2005).
2 Use of fluoridated toothpaste all dentate patients
should use toothpaste with at least 1000 ppm fluoride,
while dentate patients with radiation-induced SGD
should use specialist toothpaste with 5000 ppm
fluoride.
3 Avoidance of acidic drinks/foods/medication acidic
products will contribute to complications such as
dental erosion, dental caries and oral candidosis.
4 Avoidance of sugary drinks/foods/medication sugary
products will contribute to complications such as
dental caries and oral candidosis.
5 Avoidance of xerostomic medication it should be
noted that some oral care products contain alcohol,
which may further aggravate the situation.
6 Regular dental review patients should have regular
dental reviews (with a dentist/dental hygienist).

Consideration should be given to treatment of the

complications of the salivary gland dysfunction (grade of
recommendation D)
Adequate management of SGD may resolve some or all of
the complications. A detailed discussion about the treatment of these complications is beyond the scope of this
consensus statement, and the reader is advised to consult
an appropriate oral care textbook (Davies & Finlay 2005).

Patients with salivary gland dysfunction should be

regularly reassessed (grade of recommendation D)
The successful management of SGD depends on adequate
reassessment of the patient. The objectives of reassessment are to determine the efficacy of any intervention, the
tolerability of the intervention and whether additional
complications have developed.
Interventions that are not effective and/or not tolerated
should be discontinued. Moreover, any patient with
176

Unfortunately, most medical professionals have little

understanding about the nature of cancer-related SGD,
which results in significant under-diagnosis/undertreatment of the problem. Thus, additional educational
initiatives need to be undertaken, and these need to be
aimed at members of the oncology MDT, members of the
wider medical community (e.g. primary care professionals) and also patients and their non-professional carers.
The content/format of the educational initiatives will
obviously need to be tailored to the different groups (e.g.
professional vs. non-professional) and also to different circumstances (e.g. radiation-induced SGD vs. other causes
of SGD).

More research is required into the problem of

cancer-related salivary gland dysfunction (grade of
recommendation D)
Unfortunately, most of the recommendations in this
document are based on limited evidence (i.e. grade of recommendation D) (Harbour & Miller 2001). Thus, most of
the recommendations are based on non-analytical studies,
or simply expert opinion. Furthermore, many of the recommendations are based on studies performed in other
groups of patients, and it may not be appropriate to
extrapolate data from patients with non-malignant disease
to patients with malignant disease. Hence, additional
research is required to evaluate existing treatment interventions, and (equally importantly) to investigate novel
treatment interventions for cancer-related SGD.

SOURC E OF FUNDI NG
The development of these recommendations was supported by an unrestricted educational grant from
Nycomed, Denmark.

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