Radiation-induced xerostomia

CLINICAL REVIEW
RADIATION-INDUCED XEROSTOMIA
Mark S. Chambers, DMD, MS, 1 David I. Rosenthal, MD, 2 Randal S. Weber, MD 1
1 Department of Head and Neck Surgery, The University of Texas, M. D. Anderson Cancer Center,
1515 Holcombe Boulevard, Houston, TX 77030-4009. E-mail: mchamber@mdanderson.org
2 Department of Radiation Oncology, The University of Texas, M. D. Anderson Cancer Center,
Houston, Texas
Accepted 6 March 2006
Published online 11 August 2006 in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/hed.20456
Abstract: Background. Radiation-induced xerostomia is a frequent
and usually permanent side effect of radiation therapy for
head and neck cancer. We summarize recent developments in
the prevention and treatment of radiation-induced xerostomia.
Methods. The Medline database was searched for articles
published within the past 10 years on the prevention and treatment
of postirradiation xerostomia. Proceedings of recent important
national meetings and government Web registries of clinical
trials and therapeutic agents were also consulted. Priority was
given to randomized controlled trials but, because of the scarcity
of such trials, small open trials were included in this review.
No other predetermined selection criteria were used, although
articles exploring the effects of xerostomia and its treatment on
quality of life were considered of special interest.
Results. A variety of preventive approaches for postirradiation
xerostomia exist, involving more conformal radiation delivery
technology, radioprotective agents, and even preirradiation surgical
techniques. Therapeutic interventions include supportive
care, saliva supplementation, and the use of procholinergic salivary
secretagogues.
Conclusions. Radiation-induced xerostomia constitutes a
significant morbidity after orofacial irradiation. Careful preventive
techniques, meticulous supportive care, and new preventive
Correspondence to: M. S. Chambers
Dr. Chambers has received research support from Rx Kinetix, Inc. and
MedImmune Oncology and serves as a Consultant to Ruvelo, Inc.
Dr. Rosenthal has received research support from MGI Pharma and
MedImmune Oncology. Dr. Weber is a Consultant for Imclone/BMS.
Dr. Chambers and Dr. Weber have reported a financial interest/relationship
with Daiichi Pharmaceutical Corporation as investigators.
VC
2006 Wiley Periodicals, Inc.
and therapeutic agents may prove useful in combination.
VC 2006 Wiley Periodicals, Inc. Head Neck 29: 58–63, 2007
Keywords: xerostomia; radiation therapy; radioprotective agents;
intensity modulated radiation therapy; oral complications
The diagnosis of head and neck cancer is made
every year in approximately 30,000 to 40,000
people in the United States. 1 Many patients are
treated with therapeutic irradiation delivered to
the head and neck as sole treatment or in addition
to surgery. Radiotherapy has also been combined
with chemotherapy to sensitize locally
advanced tumors to radiation or eradicate distant
micrometastases. 2 Xerostomia is a common, distressing
side effect of radiotherapy for head and
neck cancer, occurring to some degree in up to
100% of patients undergoing such treatment. 3
Hyposalivation and the subjective perception of
oral dryness occur predictably when the major salivary
glands are included in the radiation field.
The major salivary glands are responsible for 90%
of saliva production, which in healthy individuals
averages about 1000 to 1500 mL/day.
In patients with radiation-induced salivary
gland injury, salivary flow typically decreases by
50% to 60% during the first week after 25 to 30 Gy
of standard fractionated radiotherapy has been
delivered, and basal flow reaches a nadir in 2 to
58 Radiation-Induced Xerostomia HEAD & NECK—DOI 10.1002/hed January 2007

Table I. Common Terminology Criteria for Adverse Events v3.0 grading scale for xerostomia. 13
Grade
Description
1: Mild AE Symptomatic (dry or thick saliva) without significant dietary alteration;
unstimulated salivary flow >0.2 mL/min
2: Moderate AE Symptomatic and significant oral intake alteration (eg, copious water, other lubricants,
diet limited to purées and/or soft, moist foods); unstimulated salivary flow 0.1–0.2 mL/min
3: Severe AE Symptoms leading to inability to adequately aliment orally; intravenous fluids, tube
feedings, or total parenteral nutrition indicated; unstimulated salivary flow

Recent technological advances in therapeutic
radiation delivery have allowed the sparing of a
portion of the major salivary glands. 8,17 Intensitymodulated
radiation therapy (IMRT) involves the
use of computer algorithms to adjust the dose
delivered by segments (beamlets) of the radiation
beam, so that the spatial distribution of the radiation
dose conforms tightly to the target volume,
whereas the dose to adjacent normal tissue is
minimized. 18 In a study comparing IMRT with
conventional radiation therapy, IMRT reduced
the incidence of late grade 2 xerostomia. In
patients with oropharyngeal carcinoma, the dosimetric
advantage of IMRT over conventional techniques
resulted in a significant reduction of late
salivary gland toxicity. Other reports of patients
being treated for cancers in other head and neck
sites, including the nasopharynx, have demonstrated
significant salivary sparing. 18,19 IMRT
allows relative parotid salivary gland preservation,
but the potential benefit may not be applicable
to all patients; limitations in their use arise
from the area anatomy and often from the extent
of the tumors. 17
Amifostine is a cytoprotective organic thiophosphate
that acts as a free radical scavenger. 20
Preclinical studies using a rat parotid gland model
demonstrated both short-term and long-term protection
against radiation-induced injury of salivary
glands, where amifostine accumulates preferentially.
This finding led to early clinical trials
in patients with head and neck cancer treated
with radiation therapy, in which amifostine was
reported to provide salivary gland protection. 20 A
more recent prospective phase III trial also
showed that amifostine reduced both acute and
chronic xerostomia in patients receiving radiation
therapy for head and neck cancer. 21 These findings
led the Food and Drug Administration (FDA)
to approve the use of amifostine to reduce the incidence
and severity of radiation-induced xerostomia
in patients with head and neck cancer
receiving postoperative radiation therapy in
which the radiation port includes a substantial
portion of the parotid glands. Recent American
Society of Clinical Oncology practice guidelines
also recommend that amifostine be considered for
these patients. 22,23
In the phase III study, amifostine was administered
intravenously 15 to 30 minutes before each
radiation treatment at a dose of 200 mg/m 2 .Subcutaneous
administration, although not FDAapproved,
was found in a phase II randomized
trial to be efficacious and well tolerated. 24 Common
side effects of intravenous amifostine include
nausea, emesis, and hypotension. The rates of
such high-grade symptoms are reduced significantly
by subcutaneous administration, which
has become the preferred route of administration
at many institutions. 6,9
The potential to develop other protective agents
that will prevent xerostomia instead of alleviating
its symptoms continues to be a focus of research.
This includes examining acinar cell proliferation
stimulants, metal ion mobilizers or chelators, other
free radical scavengers, and antioxidant molecules
such as a-tocopherol and b-carotene. 17
Management of Radiation-Induced Xerostomia. For
patients with radiation-induced xerostomia, treatments
are nonspecific and are directed primarily
toward alleviation of symptoms. Symptomatic
relief can be achieved by behavioral modifications,
replacement of missing saliva, and use of prosecretory
drugs. Simple, helpful measures include the
use of home humidifiers and a careful review of
patients’ medications to exclude or replace those
that exacerbate xerostomia. Patients may be encouraged
to use sugar-free tart candy or sugarfree
chewing gum to stimulate residual saliva production
and should discontinue habits that exacerbate
xerostomia, such as smoking and consuming
dairy and sugar-containing products that thicken
saliva, as well as alcohol.
Replacing saliva is important in the management
of radiation-induced xerostomia, as it provides
symptomatic relief, limits the damaging
local effects of chronic xerostomia, and preserves
QOL. 6 Artificial saliva preparations act as substitutes
for the lubricating, hydrating, and antimicrobial
actions of natural saliva. Originally designed
as aqueous ionic solutions, they have gradually
become more complex with the addition of
fluoride, carboxymethylcellulose, mucin, glycoproteins,
and antimicrobial/antifungal peptides in
various combinations. Unfortunately, the complex,
multifunctional, and overlapping nature of
saliva components has not been approached so far
by any of the numerous existing saliva replacements/substitutes.
Major limitations of saliva
substitutes include short duration of action, undesirable
taste, inconvenience, and cost. As a result,
many patients prefer to carry water to drink and
spray throughout the day. 6 Nevertheless, artificial
saliva can provide useful adjunctive therapy
under special circumstances, for example, at bedtime
and during air travel. 9
60 Radiation-Induced Xerostomia HEAD & NECK—DOI 10.1002/hed January 2007

Patients often resort to complementary and
alternative medicine for primary or adjunct
therapies. In particular, acupuncture has gained
significant momentum in current research, after
reports of successful palliation of xerostomia
appeared in the West as early as 1981. 9 A regimen
of 3 or 4 weekly sessions followed by monthly
maintenance sessions was recommended in 1
open-label study of 50 patients, although some
patients achieved lasting remission without further
therapy. 25 This approach has yet to be tested
in a prospective randomized trial.
Promising preliminary data were reported
from a group of patients with strictly defined
pilocarpine-resistant radiation-induced xerostomia.
9,25 While the precise mechanism of action of
acupuncture is still unknown, autonomic stimulation
by the acupuncture needles is presumed to be
at least partially responsible for the effect,
although different acupuncture points and techniques
have been used. 9 Other investigators have
reported equally promising results using noninvasive
transcutaneous electrical nerve stimulation
(TENS) of acupuncture points with either traditional
TENS or the newer proprietary Codetron
technique. 3
Surgical relocation of the submandibular
gland to the submental space, before radiation
therapy, was recently proposed as a novel way to
preserve salivary function and prevent xerostomia.
12,26 Approximately 200 to 300 mL/day of
saliva, or about 15% to 30% of normal daily output,
is produced by the submandibular salivary
glands. 12,26 A Canadian group has suggested that
surgically transferring the submandibular gland,
before irradiation, to the submental space, which
is shielded from all but 5% of the total radiation
dose, can preserve its function. They performed
the procedure in 24 eligible patients who maintained
a salivary flow rate, ranging from 29% to
þ12% of the preoperative rate, and good subjective
patient-benefit scores. This report represents
proof of the principle that the physical sparing of
the submandibular gland can lead to reduction of
xerostomia rates. However, the reproducibility
and safety of this procedure remain to be confirmed,
as there is a potential risk of co-transferring
tumor cells to the submental ‘‘safe haven,’’ as
occurred in 1 patient in the study. 26 The Radiation
Therapy Oncology Group is currently investigating
this technique.
The current treatment of choice for patients
with remaining functional acinar tissue involves
the use of parasympathomimetic secretagogues. 11
These agents stimulate the M3 muscarinic receptors
found in salivary glands, leading to increased
saliva secretion, and thus offer a more
physiologic treatment for the symptoms of xerostomia
than saliva substitutes. Pilocarpine is
currently the only secretagogue approved by the
FDA for the symptomatic treatment of postirradiation
xerostomia and is also approved for the
treatment of dry mouth symptoms associated
with Sjögren syndrome. 27 In a randomized controlled
trial involving 207 patients with radiation-induced
xerostomia, pilocarpine 5 mg 3
times per day (tid) improved oral dryness in 44%
of treated patients compared with 25% of placebo
recipients (p ¼ .027). Similar improvement was
seen with a dose of 10 mg tid (46, p ¼ .020). Furthermore,
patients in both treatment groups
experienced improvement in the overall condition
of xerostomia (p ¼ .010) and mouth and
tongue comfort (p ¼ .001). 28 Another study has
shown that pilocarpine can also be efficacious
when dissolved in artificial saliva and administered
in a mouth spray, provided there is residual
salivary function. 7 Pilocarpine mouthwash, when
compared in a crossover randomized study with a
mucin-based saliva substitute, was found to be
efficacious after 3 months of treatment, leading to
a mean change in the xerostomia score in 22.5% of
patients compared with 15.2% of patients using
artificial saliva alone. 27 Preliminary animal data
suggested that administration of pilocarpine
before or during irradiation could provide protection
against the development of xerostomia. 17 Subsequently,
human studies were conducted to verify
this observation; whereas the protective effect
seemed to be reproduced in a few small trials, 27,29
others failed to demonstrate either a symptomatic
improvement accompanying the maintained salivary
flow rate or any preventive action at all. 30
The use of pilocarpine may be limited in some
patients by side effects and contraindications that
stem from its fundamental mechanism of action,
muscarinic-cholinergic agonism with mild b-cholinergic
activity. The secretory activity of exocrine
glands other than the salivary glands and the
smooth muscle tone of the gastrointestinal and
genitourinary tracts are increased. 27 As a result,
the use of pilocarpine is contraindicated in patients
with uncontrolled asthma, acute iritis, and
narrow-angle glaucoma. Pilocarpine should also
be prescribed cautiously for patients with a
history of severe cardiovascular disease or with
biliary disease, gastric ulcer, nephrolithiasis,
or diarrhea. 31 The most frequent adverse effects
Radiation-Induced Xerostomia HEAD & NECK—DOI 10.1002/hed January 2007 61

associated with pilocarpine use are sweating,
nausea, and rhinitis. Less frequent are chills,
diarrhea, urinary frequency, blurred vision, dizziness,
abdominal cramps, palpitations, lacrimation,
and headaches. 31 Side effects are often doserelated:
in clinical trials. Excessive sweating
occurred in 68% of patients receiving 10 mg tid vs
29% of patients receiving 5 mg tid and 9% receiving
placebo. 31
Cevimeline hydrochloride is a newer muscarinic
agonist that was found safe and effective in
treating xerostomia associated with Sjögren syndrome
and has been FDA approved for this use. 27
Cevimeline has a selective affinity for M3 muscarinic
receptors, which are the major receptors
associated with stimulation of salivary flow. 32 In 3
clinical trials, cevimeline improved symptoms of
dry mouth in patients with Sjögren syndrome. In
the first 2 trials (involving 75 and 197 patients,
respectively), a significantly higher percentage of
patients receiving cevimeline 30 mg tid reported
improvement in the overall condition of dry mouth
compared with patients receiving placebo (p ¼
.0043 and .0004). Patients receiving cevimeline
30 mg tid in the third trial were more likely than
placebo recipients to have increased postdose
salivary flow (p ¼ .0017). Of 1777 patients with
Sjögren syndrome or other conditions treated with
cevimeline in clinical trials, 11.1% discontinued
treatment because of adverse events. Excessive
sweating, nausea, rhinitis, and diarrhea occurred
in 18.7%, 13.8%, 11.2%, and 10.3%, respectively, of
patients receiving cevimeline 30 mg tid compared
with 2.4%, 7.9%, 5.4%, and 10.3% of placebo recipients.
33–35
Recently, cevimeline was shown in animal
studies to increase salivation after head and neck
irradiation. 27 Two phase III trials including a total
of 570 patients with radiation-induced xerostomia
evaluated the efficacy and safety of cevimeline in
this population. 36 Patients were randomized to
cevimeline 30 to 45 mg tid or placebo for 12 weeks.
In 1 study, global improvement in dry mouth
symptoms was reported by significantly more
patients in the cevimeline-treated group than in
the placebo group (47.4% vs 33.3%, p ¼ .0162). In
both studies, cevimeline-treated patients had significantly
greater increases in unstimulated salivary
flow than placebo recipients at the final evaluation.
Increased sweating was the significant
adverse event reported more frequently in the
cevimeline groups than in the placebo groups. The
longitudinal safety evaluation phase of the studies
is currently in progress.
CONCLUSION
Radiation-induced xerostomia causes significant
morbidity after irradiation for head and neck cancers.
Other patients affected are those receiving
iodine 131 therapy for thyroid cancer or total body
irradiation for allogeneic stem cell transplant.
Current options for prevention and treatment
are limited. New, more selective radiation-delivery
techniques (eg, IMRT) allow some degree of
salivary gland preservation. A proposed surgical
preventive strategy, submandibular gland transfer,
may help preserve gland function after irradiation
but is still investigational. 12,26 There is
increased interest in the combined use of IMRT
and radioprotective agents: acinar cell proliferation
stimulants, metal ion mobilizers or chelators,
free radical scavengers, and other antioxidant
molecules. The FDA approved amifostine to prevent
radiation-induced xerostomia in patients
receiving postoperative radiation therapy for
head and neck cancers. Patients whose symptoms
of dryness are not optimally controlled by moisture
replacement should be considered for treatment
with secretory stimulants (secretagogues) to
stimulate the M3 muscarinic receptors found in
salivary glands, leading to enhanced secretion.
These agents include pilocarpine and cevimeline.
Furthermore, intensive ongoing research in gene
therapy, aiming to repair salivary glands damaged
by irradiation or autoimmune processes, has
produced encouraging results, establishing the
foundation of a promising future. Key to the management
of postirradiation xerostomia is symptomatic
relief with saliva supplementation/stimulation
and a multidisciplinary approach that includes
physicians of various specialties, dentists,
and even complementary and alternative medicine
modalities (eg, acupuncture or Codetron
treatments). 3,9,25
Acknowledgments. The authors thank Daiichi
Pharmaceutical Corporation for funding this
publication and IMPRINT Publication Science,
New York, for their editorial support in the preparation
and styling of this manuscript.
REFERENCES
1. National Cancer Institute Fact Sheet. Head and Neck
Cancer: Questions and Answers. Available at: www.cancer.
gov/cancertopics/factsheet/sites-types/head-and-neck. Accessed
April 12, 2006.
2. Rosenthal DI, Ang KK. Altered radiation therapy fractionation,
chemoradiation, and patient selection for the
62 Radiation-Induced Xerostomia HEAD & NECK—DOI 10.1002/hed January 2007

treatment of head and neck squamous carcinoma. Semin
Radiat Oncol 2004;14:153–166.
3. Wong RK, Jones GW, Sagar SM, Babjak AF, Whelan T.
A Phase I–II study in the use of acupuncture-like transcutaneous
nerve stimulation in the treatment of radiation-induced
xerostomia in head-and-neck cancer patients
treated with radical radiotherapy. Int J Radiat
Oncol Biol Phys 2003;57:472–480.
4. Wescott WB, Mira JG, Starcke EN, Shannon IL,
Thornby JI. Alterations in whole saliva flow rate induced
by fractionated radiotherapy. AJR Am J Roentgenol 1978;
130:145–149.
5. Liu RP, Fleming TJ, Toth BB, Keene HJ. Salivary flow
rates in patients with head and neck cancer 0.5 to 25
years after radiotherapy. Oral Surg Oral Med Oral Pathol
1990;70:724–729.
6. Taylor SE. Efficacy and economic evaluation of pilocarpine
in treating radiation-induced xerostomia. Expert
Opin Pharmacother 2003;4:1489–1497.
7. Frydrych AM, Davies GR, Slack-Smith LM, Heywood J.
An investigation into the use of pilocarpine as a sialagogue
in patients with radiation induced xerostomia.
Aust Dent J 2002;47:249–253.
8. Eisbruch A, Kim HM, Terrell JE, Marsh LH, Dawson LA,
Ship JA. Xerostomia and its predictors following parotidsparing
irradiation of head-and-neck cancer. Int J Radiat
Oncol Biol Phys 2001;50:695–704.
9. Bruce SD. Radiation-induced xerostomia: how dry is
your patient Clin J Oncol Nurs 2004;8:61–67.
10. Peterson DE. Oral problems in supportive care: no longer
an orphan topic Support Care Cancer 2000;8:347–348.
11. Atkinson JC, Baum BJ. Salivary enhancement: current
status and future therapies. J Dent Educ 2001;65:1096–
1101.
12. Jha N, Seikaly H, McGaw T, Coulter L. Submandibular
salivary gland transfer prevents radiation-induced xerostomia.
Int J Radiat Oncol Biol Phys 2000;46:7–11.
13. Cancer Therapy Evaluation Program, Common Terminology
Criteria for Adverse Events, Version 3.0, DCTD, NCI,
NIH, DHHS. March 31, 2003. Available at: http://ctep.
cancer.gov/reporting/ctc.html. Accessed January 27, 2006.
14. Epstein JB, Robertson M, Emerton S, Phillips N, Stevenson-Moore
P. Quality of life and oral function in patients
treated with radiation therapy for head and neck cancer.
Head Neck 2001;23:389–398.
15. Papas AS, Joshi A, MacDonald SL, et al. Caries prevalence
in xerostomic individuals. J Can Dent Assoc 1993;
59:171–174;177–179.
16. Oral Cancer Background Papers. National Strategic
Planning Conference for the Prevention and Control of
Oral and Pharyngeal Cancer, August 7–9, 1996, Chicago,
Illinois. Available at: http://www.cdc.gov/oralhealth/pdfs/
oc-bgpapers.pdf. Accessed May 16, 2006.
17. Nagler RM, Baum BJ. Prophylactic treatment reduces
the severity of xerostomia following radiation therapy
for oral cavity cancer. Arch Otolaryngol Head Neck Surg
2003;129:247–250.
18. Chao KS, Majhail N, Huang C-J, et al. Intensity-modulated
radiation therapy reduces late salivary toxicity without
compromising tumor control in patients with oropharyngeal
carcinoma: a comparison with conventional techniques.
Radiother Oncol 2001;61:275–280.
19. Lee N, Xia P, Quivey JM, et al. Intensity-modulated
radiotherapy in the treatment of nasopharyngeal carcinoma:
an update of the UCSF experience. Int J Radiat
Oncol Biol Phys 2002;53:12–22.
20. Bohuslavizki KH, Klutmann S, Brenner W, Mester J,
Henze E, Clausen M. Salivary gland protection by amifostine
in high-dose radioiodine treatment: results of a
double-blind placebo-controlled study. J Clin Oncol 1998;
16:3542–3549.
21. Brizel DM, Wasserman T. The influence of intravenous
amifostine on xerostomia and survival during radiotherapy
for head and neck cancer: two-year follow-up of prospective
randomized trial. J Clin Oncol 2004;22(14 suppl):
5536.
22. Schuchter LM, Hensley ML, Meropol NJ, et al. 2002
update of recommendations for the use of chemotherapy
and radiotherapy protectants: clinical practice guidelines
of the American Society of Clinical Oncology. J Clin
Oncol 2002;20:2895–2903.
23. Hensley ML, Schuchter LM, Lindley C, et al. American
Society of Clinical Oncology clinical practice guidelines
for the use of chemotherapy and radiotherapy protectants.
J Clin Oncol 1999;17:3333–3355.
24. Koukourakis MI, Simopoulos C, Minopoulos G, et al.
Amifostine before chemotherapy: improved tolerance
profile of the subcutaneous over the intravenous route.
Clin Cancer Res 2003;9:3288–3293.
25. Johnstone PA, Niemtzow RC, Riffenburgh RH. Acupuncture
for xerostomia: clinical update. Cancer 2002;94:
1151–1156.
26. Seikaly H, Jha N, McGaw T, Coulter L, Liu R, Oldring D.
Submandibular gland transfer: a new method of preventing
radiation-induced xerostomia. Laryngoscope 2001; 111:
347–352.
27. Chambers M, Garden A, Klies M, Martin J. Radiationinduced
xerostomia in patients with head and neck cancer:
pathogenesis, impact on quality of life, and management.
Head Neck 2004;26:796–807.
28. Johnson JT, Ferretti GA, Nethery WJ, et al. Oral pilocarpine
for post-irradiation xerostomia in patients with
head and neck cancer. N Engl J Med 1993;329:390–395.
29. Haddad P, Karimi M. A randomized, double-blind, placebo-controlled
trial of concomitant pilocarpine with
head and neck irradiation for prevention of radiationinduced
xerostomia. Radiother Oncol 2002;64:29–32.
30. Fisher J, Scott C, Scarantino CW, et al. Phase III quality-of-life
study results: impact on patients’ quality of life
to reducing xerostomia after radiotherapy for head-andneck
cancer—RTOG 97–09. Int J Radiat Oncol Biol Phys
2003;56:832–836.
31. Salagen tablets (pilocarpine hydrochloride) [package
insert]. Bloomington, Minn: MGI Pharma, Inc; 2003.
32. Iwabuchi Y, Masuhara T. Sialagogic activities of SNI-
2011 compared with those of pilocarpine and McN-A-343
in rat salivary glands: identification of a potential therapeutic
agent for treatment of Sjögren’s syndrome. Gen
Pharmacol 1994;25:123–129.
33. Evoxac capsules (cevimeline hydrochloride) [package
insert]. Montvale, NJ: Daiichi Pharmaceutical Corporation;
2005.
34. Petrone D, Condemi JJ, Fife R, Gluck O, Cohen S, Dalgin
P. A double-blind, randomized, placebo-controlled
study of cevimeline in Sjögren’s syndrome patients with
xerostomia and keratoconjunctivitis sicca. Arthritis Rheum
2002;46:748–754.
35. Fife RS, Chase WF, Dore RK, et al. Cevimeline for the
treatment of xerostomia in patients with Sjögren syndrome:
a randomized trial. Arch Intern Med 2002;162:
1293–1300.
36. Chambers MS, Posner MR, Jones CU, Weber RS, Vitti R.
Two phase III clinical studies of cevimeline for postirradiation
xerostomia in patients with head and neck cancer.
Presented at the 2005 Annual Meeting of the American
Society of Clinical Oncology. Abstract no. 5503. Available
at: http://www.asco.org/ac/1,1003, 12-002643-00_18-0034-
00_19-0031963,00.asp. Accessed August 15, 2005.
Radiation-Induced Xerostomia HEAD & NECK—DOI 10.1002/hed January 2007 63