Conditions Affected By Both Chemotherapy and Head/Neck Radiation
Xerostomia
Topical oral antimicrobials
Dysgeusia
Fatigue
Nutritional Compromise
Xerostomia
Xerostomia is caused by a marked reduction in salivary gland secretion [1,2] and has a significant impact on quality of life.[3]
Symptoms and signs of xerostomia include dryness, burning sensation of the
tongue, fissures at lip commissures, atrophy of dorsal tongue surface,
difficulty in wearing dentures (edentulous patients), and increased thirst.
Radiation therapy can damage salivary glands, causing xerostomia (symptoms of dry mouth) and salivary hypofunction. In addition, selected chemotherapeutic agents (singly or in combination) have been implicated in causing salivary dysfunction; however, this effect has not been well documented.
Ionizing radiation to salivary glands results in inflammatory and degenerative effects on salivary gland parenchyma, especially serous acinar cells.
Salivary flow decreases within 1 week after starting radiation treatment and xerostomia becomes apparent when doses exceed 10 Gy.
Doses larger than 54 Gy are generally considered to induce irreversible dysfunction. The degree of dysfunction
is related to the radiation dose and volume of glandular tissue in the
radiation field. Parotid glands may be more susceptible to radiation effects
than submandibular, sublingual, and other minor salivary glandular tissues.
Salivary gland tissues that have been excluded from the radiation portal may
become hyperplastic, partially compensating for the nonfunctional glands at
other oral sites.
Generally stated, some degree of salivary gland recovery is seen over the first 6 months after radiation therapy. Maximum recovery is generally reported by 12 months posttherapy, but it is usually incomplete and the overall degree of dryness can range from mild to severe. One study demonstrated successful surgical submandibular gland transfer to the submental space resulting in a functioning gland even after radiation with appropriate shielding.[4]
Xerostomia alters the mouth’s buffering capacity and mechanical cleansing
ability, thereby contributing to dental caries and progressive periodontal
disease. Development of dental caries also is accelerated in the presence of
xerostomia due to reduction in delivery to the dentition of antimicrobial
proteins normally contained in saliva.
Saliva is necessary for the normal execution of oral functions such as taste,
swallowing, and speech. Unstimulated whole salivary flow rates
less than 0.1 mL per minute are considered indicative of xerostomia (normal salivary flow
rate = 0.3–0.5 mL/minute). Xerostomia produces the following changes in the
mouth that collectively cause patient discomfort and increased risk for oral
lesions:
- Salivary viscosity increases, with resultant impaired lubrication of
oral tissues.
- Buffering capacity is compromised, with increased risk for dental caries.
- Oral flora becomes more pathogenic.
- Plaque levels accumulate due to the patient’s difficulty in maintaining
oral hygiene.
- Acid production after sugar exposure results in further demineralization of
the teeth and leads to dental decay.
Patients who experience xerostomia must maintain excellent oral hygiene to
minimize risk for oral lesions. Periodontal disease can be accelerated and
caries can become rampant unless preventive measures are instituted. Multiple
preventive strategies should be considered (refer to the list on the Oral and Dental Management of the Xerostomic Patient below). The following is an example of a patient
protocol:
Perform systematic oral hygiene at least 4 times a day (after meals and at bedtime):
- Use a fluoridated toothpaste when brushing.
- Apply a prescription-strength fluoride gel at bedtime to clean teeth.
- Rinse with a solution of salt and baking soda 4 to 6 times a day (½
tsp salt and ½ tsp baking soda in 1 cup warm water) to clean and
lubricate the oral tissues and to buffer the oral environment.
- Avoid foods and liquids with a high sugar content.
- Sip water to alleviate mouth dryness.
Oral and Dental Management of the Xerostomic Patient [2]
- Plaque removal:
- Tooth brushing.
- Flossing.
- Other oral hygiene aids.
- Remineralizing solutions:
- Fluoride and calcium/phosphates.
- Topical high concentration fluorides.
- Children: topical and systemic.
- Adults: topical.
- Topical antimicrobial rinses:
- Chlorhexidine solutions/rinses (Peridex).
- Povidone iodine oral rinses.
- Tetracycline oral rinses.
- Sialogogues:
- pilocarpine
(Salagen)
- cevimeline (Evoxac)
- bethanechol
- antholetrithione (Sialor)
[Note: Prescription-strength fluorides should be used because nonprescription fluoride
preparations are inadequate in the face of moderate-to-high dental caries risk.
If drinking water does not have adequate fluoride content to prevent dental
decay, then oral fluoride (i.e., drops, vitamins, etc.) should be provided.]
Use of topical fluoride has demonstrable benefit in minimizing caries
formation. During radiation treatment, it has been recommended that topical 1%
sodium fluoride gel be applied daily into mouth guards that are placed over the upper and lower teeth. The appliances should remain in place
for 5 minutes, after which the patient should not eat or drink for 30 minutes.
Management of xerostomia also includes use of saliva substitutes or
sialagogues. Saliva substitutes or artificial saliva preparations (oral rinses
containing hydroxyethylcellulose, hydroxypropylcellulose, or carboxymethylcellulose) are
palliative agents that relieve the discomfort of xerostomia by temporarily
wetting the oral mucosa. Sialagogues pharmacologically stimulate saliva
production from intact salivary glandular tissues.[1,5] Submandibular gland transfer has been used for xerostomia.[6]
Pilocarpine is the only drug approved by the U.S. Food and Drug Administration
for use as a sialogogue (5-mg tablets of pilocarpine hydrochloride) for radiation xerostomia. Treatment
is initiated at 5 mg by mouth 3 times a day; dose is then titrated to achieve
optimal clinical response and minimize adverse effects. Some patients may
experience increased benefit at higher daily doses; however, incidence of
adverse effects increases proportionally with dose. The patient’s evening dose
may be increased to 10 mg within 1 week after starting pilocarpine.
Subsequently, morning and afternoon doses may also be increased to a maximum 10
mg per dose (30 mg/day). Patient tolerance is confirmed by allowing 7 days between
increments. The most common adverse effect at clinically useful doses of
pilocarpine is hyperhidrosis (excessive sweating); its incidence and severity
are proportional to dosage. Nausea, chills, rhinorrhea, vasodilation,
increased lacrimation, bladder pressure (urinary urgency and frequency),
dizziness, asthenia, headache, diarrhea, and dyspepsia are also reported,
typically at doses higher than 5 mg 3 times a day. Pilocarpine usually
increases salivary flow within 30 minutes after ingestion. Maximal response may occur only after continual use. In a randomized study of 249 patients with head and neck cancer, however, the concomitant use of pilocarpine during radiation did not have a positive impact on quality of life or patient assessment of salivary function despite the maintenance of salivary flow.[7]
Cevimeline (30 mg 3 times a day) also appears anecdotally to have efficacy in managing radiation-induced xerostomia. Although to date cevimeline is only approved for use in the management of Sjögren syndrome, appropriate clinical trials are under way and its efficacy should soon be established. While cevimeline has greater selective affinity for M3 muscarinic receptors than pilocarpine, whether this can prove advantageous for treating radiation xerostomia remains unclear.
Amifostine is an organic thiophosphate approved for the protection of normal tissues against the harmful effects of radiation or chemotherapy, including reduction of acute or late xerostomia in patients with head and neck cancer. Studies have reported varying degrees of effectiveness.[8,9] One randomized prospective study reported that intravenous amifostine administered during head and neck radiation therapy reduces the severity and duration of xerostomia 2 years after amifostine treatment, without apparent compromise of locoregional tumor control rates, progression-free survival, or overall patient survival.[10]
Topical oral antimicrobials
Oral antimicrobials may also be of value. For example, chlorhexidine gluconate
is a broad spectrum antimicrobial with in vitro activity against gram-positive
and gram-negative organisms, yeast, and other fungal organisms. It also has
the desirable properties of sustained binding to oral surfaces and minimal
gastrointestinal absorption, thereby limiting adverse systemic effects.
Use of chlorhexidine gluconate in the prophylaxis of oral infections shows promise in reducing
inflammation and ulceration, as well as in reducing oral microorganisms in
high-risk patient groups. Chlorhexidine gluconate 0.12% oral rinse may be used
in conjunction with prophylactic topical and systemic antimicrobials in the
high-risk patient populations. Chlorhexidine oral rinse has been used in
combination with fluoride gel to control cariogenic flora. Chlorhexidine oral
rinse may be used as a mouthwash and gargle, but should not be ingested.
Commercially marketed formulations may also contain appreciable quantities of
alcohol, which may exacerbate xerostomia. This may be particularly important
since xerostomia may cause a shift toward a more cariogenic flora.
Dysgeusia
Dysgeusia can be a prominent symptom in patients who are receiving chemotherapy or head/neck radiation.[11-16] Etiology is likely associated with several factors including
direct neurotoxicity to taste buds, xerostomia, infection, and psychologic
conditioning.
Patients receiving cancer chemotherapy may experience unpleasant taste
secondary to diffusion of drug into the oral cavity. In addition, chemotherapy
patients often describe dysgeusia in the early weeks after cessation of the
cytotoxic therapy. The symptom in general is reversible, however, and taste
sensation returns to normal in the ensuing months.
By comparison, however, a total fractionated radiation dose higher than 3,000
Gy reduces acuity of sweet, sour, bitter, and salt tastes. Damage to the
microvilli and outer surface of the taste cells has been proposed as the
principal mechanism for loss of the sense of taste. In many cases, taste
acuity returns in 2 to 3 months after cessation of radiation. However,
many other patients develop permanent hypogeusia. Zinc supplementation (zinc
sulfate 220 mg 2 times a day) has been reported to be useful in some patients;
the overall benefit of this treatment remains unclear.[17-19]
Fatigue
Cancer patients undergoing high-dose chemotherapy and/or radiation can
experience fatigue related to either disease or its treatment.[20] These
processes can produce sleep deprivation or metabolic disorders which
collectively contribute to compromised oral status. For example, the fatigued
patient will likely have impaired compliance with mouthcare protocols designed
to otherwise minimize risk of mucosal ulceration, infection, and pain. In
addition, biochemical abnormalities are likely involved in many patients. The
psychosocial component can also play a major role, with depression contributing
to the overall status. (Refer to the PDQ summary on Fatigue for more
information.)
Nutritional Compromise
Patients with head and neck cancer are at high risk for nutritional problems. The malignancy itself, poor nutrition before diagnosis, and the complications of surgery, radiation, and chemotherapy all contribute to malnutrition.[21] In cancer patients, loss of appetite can also occur secondary to mucositis, xerostomia, taste loss, dysphagia, nausea, and vomiting. Quality of life is compromised as eating becomes more problematic. Oral pain with eating may lead to selection of foods that do not aggravate the oral tissues, often at the expense of adequate nutrition. Nutritional deficiencies can be minimized by modifying the texture and consistency of the diet and by adding more frequent meals and snacks to increase calories and protein. Ongoing nutrition assessment and counseling with a registered dietitian should be part of the patient’s treatment plan.[22]
Many patients who receive radiation therapy alone are able to tolerate soft foods; however, as treatment progresses, most patients must transition to liquid diets using high-calorie, high-protein liquid nutritional supplements, and some may require enteral feeding tubes to meet their nutritional needs. Almost all patients receiving concurrent chemotherapy and radiation therapy will become fully dependent on enteral nutritional support within 3 to 4 weeks of therapy. Numerous studies have demonstrated the benefit of enteral feedings initiated at the onset of treatment, before significant weight loss has occurred.[23,24]
Oral nutrition is reinstituted after treatment has concluded and the radiated site has adequately healed. Oral nutrition often requires a team approach. The assistance of a speech and swallowing therapist to assess for any swallowing dysfunction resulting from surgery or treatment is often necessary and beneficial in easing the transition back to solid foods. The number of tube feedings can be decreased as a patient's oral intake increases, with tube feeding being discontinued when 75% of a patient's nutrition needs are being met orally. Although most patients will resume adequate oral intake, many will continue to experience chronic complications such as taste changes, xerostomia, and varying degrees of dysphagia that can affect their nutritional status and quality of life.[21,22]
References
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