Mouth Sores: Causes, Treatments,
     and Potential New Treatments

This original research article is a provided as a free service of
The Cure Our Children Foundation

By Jennifer Hicks

[Note: This article was written on April 27, 2003 and is for educational purposes only. It cannot be used for diagnosing or treating a health problem or a disease. If you have or suspect that you or your child may have a health problem, you should consult your doctor.  It has been reviewed by Barry Sugarman and Dr. Lainie Shapiro. All hyperlinks, even those that lead to other lead to different sections of this article, will open in a new browser window. To return here, just close the new window when done.]

mouth sores | prevent infection | traditional drugs | pain relief | natural relief | diet | investigational treatments |

The What and Why of Mouth Sores

Stomatitis, or redness and swelling in the mouth and throat, can be caused by chemotherapy and radiation. Sometimes, this also leads to mucositis, or mouth sores and ulcers.1 Either of these conditions can interfere with eating, drinking, and daily life. For the person with cancer, either condition can also lead to a risk of increased infection, a decrease in nutritional intake, and a delay in cancer treatments. Either one also makes the person affected feel pretty lousy.

The sores can appear five to 10 days 1, 2 after chemotherapy begins and their “severity and frequency depends on the specific chemotherapy” used according to Susan Shurin, MD and chief of the pediatric hematology/oncology division at the Rainbow Babies and Children's Hospital in Cleveland, OH.3

Oftentimes, patients need high-dose chemotherapy, or combined chemotherapy and radiation in preparation for stem cell or bone marrow transplants. Such high doses wipe out the bone marrow and this increases the likelihood of mouth sores.

Chemo drugs that can often cause sores are anti-tumor and antibiotic agents like doxorubicin, or vincristine, or taxoids like docetaxel may also cause them.2, 5 Other drugs such as anti-metabolites such as 5-FU and methotrexate. 4, 5 So, too, can radiation in the head or neck area. Compounding the problem is the normal bacteria and fungi in the mouth that can aggravate the condition.3, 6 Candidiasis, or thrush, is a particularly bothersome fungus.

Both chemotherapy and radiation attack cells during their division process.7, 8 Thus, cells that divide rapidly, such as those in the lining of the mouth which divide every three days,3 are often affected. This can create mouth sores because the cells that are attacked die and do not regenerate. When they don't regenerate, mouth ulcers result. Also, a diminished white blood count can make the sores appear more frequently and also increases the risk of infection.2

 

What Mouth Sores Do

Mouth sores can cause significant pain and make it difficult to eat and drink. They also increase the risk of infection. If the sores are severe, cancer therapy may need to be interrupted. In some cases, hospitalization is needed to help manage pain and keep the patient hydrated.2, 9

If there is no infection, the mouth sores often heal on their own within two to four weeks.2, 10 In some patients, though, the sores may not heal until two to four weeks after all cancer therapy has stopped. 9

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Minimizing Infection of Mouth Sores

All agree that keeping the mouth clean is the best way to prevent infection if mouth sores occur.

 

The Importance of Cleaning

Infections complicate the lives of those undergoing chemotherapy and radiation. Since the mouth naturally harbors bacteria and fungi, it’s important to keep the mouth very clean in an effort to prevent infections. The frequency of care is the most important factor in lessening the severity of and in promoting healing of the sores.24

The teeth and mouth should be cleaned every 4 hours (or after each meal) and at bedtime.3

 

Routine Oral Care During Chemotherapy and Radiation

Brushing

Teeth should be brushed gently, paying attention to the gum-line, two to three times a day with a soft, nylon bristled brush with two or three rows. Electric and ultrasonic brushes may be used in some cases if they don’t cause trauma to the mouth.25, 26 Some health care professionals, though, say it's better not to use a brush to lessen the chances of bleeding and infection. They prefer using a foam brush or piece of gauze instead.25, 26 The gauze can be soaked in salt water or an anti-microbial rinse. And, if the platelet count is less than 20,000 or if the absolute neutrophil count (ANC) is less than 500, either the foam brush or gauze should be used instead.25

If a toothbrush is used, try to alternate between two toothbrushes. After use, clean with bleach, then wash with water and dry.25 Mix one part bleach with four parts water and soak the brush for 20 hours. Or soak it in Peridex® for 20 hours.83 [Peridex® is available by prescription and can be ordered online from places such as Drugstore.com or you can call Drugstore.com at 1-800-378-4786.]

Any non-peroxide, non-tartar control, fluoride toothpaste can be used if tolerated.25 Make sure to rinse frequently during the brushing.

Some doctors may prescribe special antibacterial mouth rinses like Peridex® to get rid of bacteria and keep infection down. This is a chlorhexidine-based27 product. However, there are conflicting reports about the effectiveness of such rinses25, 28, 29, 30, 31 and, they don’t taste very good. You may want to ask if a 0.63% stannous fluoride mouth rinse like Stanimax Perio Rinse® or PerioMed® could be used instead.26, 84 The stannous part of the fluoride in each of those is considered to be antibacterial.84, 85 [Peridex® is available by prescription at most drugstores. Stanimax® and PerioMed® , also prescription drugs, are available through your dentist.]

Flossing

If the child is used to flossing, use waxed or taped floss to help prevent damage to soft tissue.25 If ANC is 500 or less, do not floss. 71

 

Special Mouth Care When Sores Are Present

Keep mouth and lips hydrated.23

Lips

Use a water- or lanolin-based moisturizer for comfort.1, 25 Some people have found that vitamin E oil applied on the lips (not in the mouth) can help heal sores on the lips.32, 52 We do not recommend use of lip balms that contain mineral oil. You may want to try Lip Shtick®, a beeswax and corn -oil based product available at health food stores or from online companies such as the Vitamin Shoppe [The Vitamin Shoppe, phone: (800) 223-1216. fax: (800) 852-7153. Web site: http://www.vitaminshoppe.com].

Brushing

Try gentle brushing with salt and baking soda. Mix 1/2 teaspoon of salt and two tablespoons of baking soda in one quart of warm water. If the sores have become crusty, try hydrogen peroxide mixed with an equal amount of water or weak salt water. This will keep the sores from healing, so only use for a day or two.1

If the toothbrush is uncomfortable or causes bleeding use a foam brush covered with gauze that’s been soaked in a salt water mix.2

Rinsing

Salt water rinses make the mouth more alkaline and thus reduces the growth of bacteria. Fluoride rinses and gels work against a build up of bacteria.36, 84, 85A salt water rinse can be made by mixing 1/2 teaspoon of salt with one cup of water.71

Sometimes, dried secretions stick to the inside of the mouth. Rinsing with a baking soda solution can remove them. Use one teaspoon of baking soda to one pint of water33 or use a product such as Alkalol®2 and gently rinse several times a day. [Alkalol® can be ordered by your pharmacist. It's made by the Alkalol Company in Taunton, MA. Phone: (508) 823-3257.] Rinsing keeps particles and bacteria from building up and compounding the problem. If sucralfate (Carafate®) is prescribed, ask if salt water can be used instead since recent studies indicate they are equally as effective and salt water is less costly.34 Some people also find Biotène products helpful. They contain no alcohol and so do not hurt when used. [Biotène, St. Louis, MO. Phone: 314-429-1000 x 22. Fax: 314-429-8626. Web site: http://www.biotenekits.com/.]

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Antivirals and Antibacterials to Prevent Infection

"Our best treatments simply avoid secondary infection [thrush or blood infection] using antifungal and sometimes antiviral medicines," says W. Mark Roberts, MD.69

Nystatin - Nystatin (Nystex®, Mycostatin®, Nilstat®) is a prescription rinse meant to be swallowed. It's often called "swish and swallow." It works against various yeasts and yeast-like fungi.2 They have been used with mixed results.37 Amphotericin (Fungizone®) rinses might also be used in place of nystatin.2

Acyclovir - (Zovirax®) While some say patients experience less pain and faster resolution of sores when acyclovir is used within 48 hours of eruption,2 others say its effectiveness has been limited. However, work is being done to create a different form of it to make it more effective. Acyclovir also comes as a topical cream, a capsule, and in injectable forms. A recent study suggests that oral valacyclovir (Valtrex®), because it is administered less frequently, may offer an advantage over acyclovir.70

Clotrimazole - Clotrimazole (Lotrimin®, Mycelex®) is an antifungal that may be used to help prevent sores.2, 6 Usually the tablet is put in the mouth and allowed to dissolve. This can be difficult for those who have a dry mouth.6 Recent studies using a clotrimazole lozenge have been conducted, but results seem to indicate the lozenge does not affect the severity of the sores.72

Fluconazole - Fluconazole (Diflucan®), another antifungal, generally is not used to prevent a yeast infection but rather to treat a suspected yeast infection.2 It is also sometimes used to reduce the frequency of sores.73 Some studies indicate that clotrimazole and fluconazole are equally as effective.58 And a relatively recent study suggests that although fluconazole and amphotericin are equal in their cure rates, fluconazole may cure the sores more quickly.74

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Mild Pain Relief - Rinses

MBX Rinses with Lidocaine

For topical relief, lidocaine may be applied directly to the sore areas.25 Lidocaine is an anesthetic or pain reliever. Alternatively, a “magic” rinse can be made of 2% viscous lidocaine (Xylocaine®) and equal amounts of diphenhydramine hydrochloride (Benadryl®) and Kaopectate®,25 Mylanta® or Maalox®.2, 24 These last four ingredients are all available over-the-counter at most drug stores. If used as a rinse, rinse for 30 seconds and then spit out.25 If the ulcerations lie beneath the mouth's lining, though, this rinse may not be effective since the anesthetic can't pass through the skin.30 Remember that lidocaine may numb the area, so be careful eating and drinking to prevent burning and choking.36   [If you have specific questions about Maalox, you can call 800-548-3708. Information about the other products is available at the Web sites each is linked to.]

Allopurinol and Vitamin E

Allopurinol (Zyloprim®) mouth rinses and vitamin E may help decrease the severity of the sores,30, 38, 64 but there have been no clinical trials to prove this yet.39 If the allopurinol is used, it’s recommended that patients dissolve a 300-mg allopurinol tablet in 60 mL of water and then rinse and spit four times a day once the first sore has started. Continue for three to five days.40

Mixtures That Can Be Compounded

Compounding is the process of mixing several ingredients. Often, mouth rinses are compounded by mixing an antibiotic, an antihistamine, and antifungal, and/or a local anesthetic.93 Tetracycline is the antibiotic most often used, but as Elyse Filderman, a pharmacist at Compounding Pharmacy of Beverly Hills, CA notes, this is not a wise option for children since it can discolor the teeth.94 An option might be erythromycin.93 If the taste is unpleasant, a flavoring can also be added.93 This type of mixed-ingredient rinse "can be pretty effective depending on the severity" of the sores, according to Filderman. (See more about compounding, below.)

Vancomycin (Vancocin®) - “Oral swishes with vancomycin seem to be effective” in minimizing infection and in providing some measure of pain relief, according Santhanam Suresh, MD, anesthesiologist and co-director of the Pain Management Service at Children's Memorial Hospital in Chicago, IL.41 Vancomycin is an antibiotic and in combination with a mouth rinse of choice adds additional protection against bacterial infection.42 This is a rinse and spit mouthwash. Vancocin® is produced by Lilly Pharmaceuticals. (Web site: http://www.lilly.com. Phone: 800-545-5979.)

Gel Films - A gel that films the sores may also provide temporary relief. Hydroxypropyl cellulose gel with benzocaine has been shown to effectively reduce the pain of mucositis for up to three hours.43, 44

Sucralfate (Carafate®) - Some doctors, such as John Murren, MD at the Yale-New Haven Medical Center,35 use rinses made from sucralfate when needed. Other healthcare practitioners simply use the sucralfate pill dissolved in two or three teaspoons of water and rinse with that.24 More information about Carafate® is available at http://www.sucralfate.com/index.html.

Other

Granulocytemacrophage colony-stimulating factor (GM-CSF) - GM-CSF is a protein made naturally as well as in labs through recombinant DNA processing45 It reacts to inflammatory agents46 and may enhance the recovery of white blood cells. 45, 47, 48 Some studies indicate that patients using oral GM-CSF mouthwash developed significantly less pain during combined chemotherapy and radiation treatments.49, 50 In one phase III clinical trial, researchers compared GM-CSF with sucralfate and found that the sores tended to be less severe in the GM-CSF51 But there are conflicting studies as to whether it may reduce the frequency or duration of the sores.12, 59, 60 One study found that the GM-CSF mouthwash did not make a difference for those receiving stem cell transplants.61, 62

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Natural Pain Relief

Aloe Vera

Debbie Markel, certified herbalist and certified natural health professional in Powhatan, VA says "aloe vera used as a mouthwash is very effective for mouth sores and mouth ulcers [since] it's particularly known for its ability to heal burns."87 She suggests that aloe vera juice be used, with a little honey to help the taste. (See note about honey below.) She also added that it should be swished and spit since it can cause diarrhea if swallowed. Aloe vera juice can be ordered from the Vitamin Shoppe or found at health food stores. [The Vitamin Shoppe, phone: (800) 223-1216. fax: (800) 852-7153. Web site: http://www.vitaminshoppe.com.]

German Chamomile

Although there is no clinical evidence to prove its effectiveness,67 some naturalists such as Kathleen Duffy, licensed practical nurse, medical herbalist, and instructor in Chicopee, MA find that German chamomile (Matricaria recutitia), which tastes a bit like apple, can provide significant relief. However, Duffy warns that the child should be checked for allergies to ragweed first. If there is an allergy, don't use it. And if you do use it, make sure it comes from a reputable source such as an herbal store.68 (Or order online from The Herbarium in Chicopee, MA (Web site: http://www.theherbarium.com/. Phone: 413-598-8119.)

Duffy has had success in decreasing the size and severity of sores by using German Chamomile as a mouthwash. She takes two tablespoons of just the flowers and adds them to one cup of boiling water - in stainless steel pan - then covers it and lets it steep and cool. When done, she strains it and it's ready to be used as a rinse and spit mouthwash. A bit of beekeeper-quality honey can be added for taste and antibacterial effect if the child is not undergoing bone marrow transplant and is over age two. German chamomile tea bags can also be used. Run them under water until soft, then tuck between the cheek and gum. Or, make chamomile ice cubes and ice pops by mixing one heaping teaspoon of the herb with one cup water and freezing.68

Glutamine

Some doctors, including Susan Shurin3 and W. Mark Roberts69 have found that glutamine, an amino acid, might help prevent mouth sores and inflammation of the mouth and throat.15, 16, 17 Although glutamine’s effectiveness has not yet been proven, Dr. Robert's is encouraged by the recent studies.69 Dr. Shurin finds that many of her pediatric patients do benefit from glutamine during therapy. Dosages vary between 24 and 30 grams per day; the usual dosage is 0.5 gram per kilogram of weight.97, 98 Ask your doctor how much is best. There’s currently a clinical trial in Phase II. 3, 18 For information about the trial, contact Dorothy Austin at the University of Kansas Medical Center. Phone: 913-588-3643. Email: daustin@kumc.edu. Glutamine is easily available in most pharmacies or can be ordered from The Vitamin Shoppe (Web site: http://www.vitaminshoppe.com. Phone: (800) 223-1216. fax: (800) 852-7153.)

Ice

Others believe that sucking on ice chips before, during, or right after the chemotherapy session might minimize the severity of the sores,22 particularly if 5-FU is the chemotherapy drug being used.23

Licorice

Karta Purkh Singh Khalsa, a contributor to the American Herbalists Guild's Herbal Education Handbook, is a natural healing specialist with more than 25 years of experience with medicinal herbs. He suggests using a mouthwash made from licorice root. The sweet tasting ingredients in licorice root are "fifty times sweeter than sugar," says Khalsa, so brew a tea with only about a teaspoon of chopped or powdered herb per one cup of water. Rinse for two or three minutes, and then spit out.90  Whole licorice root can affect the endocrine system according to Khalsa, so he suggests using it limited quantities.  DGL (Deglycyrrhizinated Licorice), a type of processed licorice root that has the endocrine constituent removed, is available in wafers.  Chew the wafers to heal oral tissues.  The root powder can be found at many herb stores or can be ordered online from The Herbarium in Chicopee, MA (Web site: http://www.theherbarium.com/. Phone: 413-598-8119) .  DGL products are available at health food stores or from online companies such as iHerb [iHerb Inc., phone: 888-792-0028, or 626-358-5678,  fax: 626-303-7275. Web site: http://www.iherb.com].

Sage

Markel, the herbalist, also suggests chewing fresh sage leaves to help heal the mouth sores.87 One or two leaves can be chewed for five to ten minutes and then discarded. Doing this "two or three times daily is plenty," she says. Do not exceed this dose, and do not take if you have epilepsy.

A sage tea can also be made and used as a gargle or mouth rinse. To make the tea, steep one teaspoon of dried herb or two teaspoons of fresh herb in one cup of boiling water for 20 minutes. Linda Kingsbury, Ph.D.,and member of the American Herbal Guild, says that thyme and white yarrow flowers can also be used. "The astringent nature of these herbs," she says, "tightens the mouth tissues reducing inflammation and preventing infection."89

You can grow your own herbs or find that at many herbal stores. They can also be ordered online from The Herbarium in Chicopee, MA (Web site: http://www.theherbarium.com/. Phone: 413-598-8119) or through Spirit Herbs in Moscow, Idaho (Web site: http://www.spiritherbs.com. Phone: 208-883-9933).

Traumeel S®

An August 2001 study indicates that a homeopathic product called Traumeel S® may reduce significantly the severity and duration of chemotherapy-induced stomatitis in children undergoing bone marrow transplantation.80 It sold in Germany, Austria, and Switzerland and contains extracts from several plants and minerals including arnica, St. John's wort, and echinacea.79 Traumeel S can be ordered from Nature's Distributors, Inc., in Fountain Hills, AZ (phone: 800-624-7114).

Vitamin E

Some studies suggest that doses of vitamin E might help prevent or alleviate the pain of mouth sores. 19, 20 One suggests that a mouth rinse with vitamin E in it can reduce the severity of mouth sores by as much as 36 percent.21 Another suggests that applying one mL of topical vitamin E (400 IU) oil may decrease the duration of the sores.86

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Severe Pain Relief

Sometimes the sores are so painful episodes, such as oral or intravenous morphine or fentanyl, are needed.41, 75 Sometimes a patient-controlled analgesia pump is used so the child can administer the medicine as needed.75, 78 Some studies suggest that applying the opioid topically, such as in a mouthwash, is also effective.76, 77 In one particular study a 0.2 percent morphine mouthwash was compared to the more traditional "magic" rinse. The rinse was made by diluting 2000 mg morphine chlorhydrate in 1000 mL of water.99 The study's author, found that a 30 mg dose every three hours (the equivalent of 15 mL mouthwash containing 30 milligrams of morphine ) was most effective and lessened severe pain by three and a half days and decreased the time of "severe functional impairment" by five and a half-days.96, 99, 100 Certainly, a topical application is worth exploring since less of the drug would enter the system. When taken orally or by injection, opioids suppress the respiratory system and may cause constipation.

 

When Drugs Don't Work or Aren't Tolerated

Compounding pharmacists, "the specialists in solving special medication problems in special populations," according to Leo Blais, R. Ph. at Pawtuxet Valley Prescriptions in Coventry RI, are the ones who can help when medications aren't tolerated or don't seem to work. In conjunction with the oncologist, compounding pharmacists create new mixtures of medication or find new ways to get them into the body. For instance, some capsulized medication can be made into a liquid and some liquids like diphenhydramine can be made into transdermal gels that can be applied to the skin rather than swallowed.81

Blais says that one particularly popular compound is based on the Stanford (or "magic") Mouth Rinse. The base of the rinse usually includes an antacid, diphenhydramine, a steroid, and nystatin. To that, different ingredients can be added according to the oncologist's instructions and child's needs. Typical additions might include 2% to 4% lidocaine or beta-D-glucan, which seems to have some healing properties.81, 82

To find your own compounding pharmacist contact the International Academy of Compounding Pharmacists in Sugar Land, TX. (Web site: http://www.iacprx.org. Phone: 800-927-4227.)

 

Diet

A bland, soft diet is recommended and the mouth should be kept moist. This can be done by frequent sips of water, or the use of ice chips or popsicles. Patients with severe sores may require intravenous feeding.

Bland diets are mostly soft, non-fatty foods like mashed potato, eggs, lean meats, and breads. Avoid acidic, spicy, salty, coarse, and dry foods.2 This includes orange juice, tomatoes, chocolate, fried foods, and carbonated beverages.95 Also, avoid any products that have an alcohol base. 35

Examples of bland, soft diets include and can be found at the NIH and Dietsite.com. You can call the NIH National Cancer Institute at 800-4-CANCER.

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Investigational Treatments

Currently there is no known method of preventing mouth sores caused by chemotherapy or radiation. There are, though, several approaches under investigation. You can also stay up to date on new trials as they become available. Visit CenterWatch.com for trial updates. Go to http://www.centerwatch.com/patient/studies/area12.html and using the pull-down menu labeled 'select a medical condition', click on mucositis. This will give a listing of all current trials. Or, go to http://www.clinicaltrials.gov/ and type mucositis or stomatitis into the search box for a listing of current trials. CenterWatch can be reached at 800-765-9647. Clinical Trials can be reached at 888-FIND-NLM.

CG53135

A new drug, Curagen's CG53135, was given FDA approval on March 3, 2003 to begin multi-center Phase I clinical trials to evaluate its safety in patients at risk for oral mucositis caused by chemotherapy or radiation.53 The drug, in pre-clinical trials was tested on animals with inflammatory bowel disease, researchers saw a decrease in the severity and extent of mucosal tissue damage.54

CG53135, also called FGF20, is a protein identified in the human genome.55 It is a member of the fibroblast growth factor-20 family, a family of human proteins. It plays important roles in how our cells are shaped and differentiated, the development of new blood vessels, tissue remodeling, inflammation and formation of tumors.56

The company has not yet announced where the trials will take place. [Curagen, Inc. New Haven, CT. phone: 888-GENOMICS. Web site: http://www.curagen.com]

Aesgen-14 (AES-14)

AES-14 is a proprietary mouth rinse suspension used two or three times a day during chemotherapy. It has been effective in clinical trials at significantly reducing the emergence, severity, and duration of mucositis. On February 4, 2003, FDA gave Aesgen's drug fast track status The Company is in Phase III clinical trials in the U.S. and overseas. Aesgen plans to submit a New Drug Application later this year.57 [Aesgen Pharmaceutical Inc, Princeton, NJ. Phone: 609-419-1090. No Web site.]

Light-Emitting Diode Therapy

Recent studies suggests that light-emitting diode (LED) therapy may be useful in the preventing mouth sores in children undergoing bone marrow transplants.11, 12 LED was originally developed for NASA plant growth experiments in space. Some research indicates that delivering light deep into tissues of the body promotes wound healing and human tissue growth.13 Clinical trials for the procedure are currently in phase II and patients aged two to 18 are being recruited. 14 [For more information about the trials, see Clinicaltrials.gov or contact Harry T. Whelan, MD  in Milwaukee, WI. Phone: 414-456-4090. Email: hwhelan@mcw.edu]

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Page last updated on May 20, 2003.

Jennifer Hicks is president of WordsWork Consulting, Inc, a firm that specializes in creating Web content - particularly for the healthcare industry. She has written more than 700 articles about healthcare, multicultural and women's issues, human resources, and education.

This site is not intended to provide legal advice or legal opinions.  If you need legal advice or opinions, please consult your attorney.

 

References

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14. "Light-Emitting Diode Therapy in Preventing Mucositis in Children Receiving Chemotherapy With or Without Radiation Therapy Before Bone Marrow Transplantation Study." Clinical Trials. http://www.clinicaltrials.gov/ct/gui/show/NCT00036712?order=15.

15. Anderson PM et al. "Oral glutamine reduces the duration and severity of stomatitis after cytotoxic cancer chemotherapy." Cancer 1998 Oct 1;83(7):1433-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9762946&dopt=Abstract.

16. Anderson PM et al. "Effect of low-dose oral glutamine on painful stomatitis during bone marrow transplantation." Bone Marrow Transplant 1998 Aug;22(4):339-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9722068&dopt=Abstract.

17. Huang EY et al. "Oral glutamine to alleviate radiation-induced oral mucositis: a pilot randomized trial." Int J Radiat Oncol Biol Phys 2000 Feb 1;46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10701731&dopt=Abstract.

18. "Glutamine in Treating Mucositis Caused by Radiation Therapy in Patients With Newly Diagnosed Cancer of the Mouth or Throat Study." Clinical Trials. http://www.clinicaltrials.gov/ct/gui/show/NCT00006994?order=7.

19. Lopez I et al. "Treatment of mucositis with vitamin E during administration of neutropenic antineoplastic agents." Ann Med Interne (Paris) 1994;145(6):405-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7864501&dopt=Abstract.

20. Osaki T et al. "Prophylaxis of oral mucositis associated with chemoradiotherapy for oral carcinoma by Azelastine hydrochloride (Azelastine) with other antioxidants." Head Neck 1994 Jul-Aug;16(4):331-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8056578&dopt=Abstract.

21. Ferrerria Paolo. "Protective Effect Of Vitamin E (VE ) In Head And Neck Cancer Radiation Induced Mucositis: A Double-Blind Randomized Trial". OncoLink Coverage of ASCO, ASH and ASTRO Meetings. May 21, 2002. http://www.oncolink.com/conferences/article.cfm?c=3&s=18&ss=125&id=604.

22. Virtual Hospital. "Chemotherapy: Treating Cancer Mouth Care." University of Iowa. 1996.http://www.vh.org/adult/patient/cancercenter/chemotherapy/mouthcare.html.

23. National Cancer Institute. "NCI/PDQ® Health professionals: Oral Complications of Chemotherapy and Head/Neck Radiation." January 16, 2003 http://www.oncolink.com/coping/article.cfm?c=5&s=27&ss=148&id=802#Management%20in%20mucositis.

24. Kaney ML et al."Stomatitis." University of Iowa. http://www.nursing.uiowa.edu/sites/PedsPain/GenePain/Stomatte.htm. Accessed April 3, 2003.

25. Rankin K, DDS et al. Editors. "Oral Health in Cancer Therapy: A Guide for Health Care Professionals." Texas Cancer Council. 1999. http://www.doep.org/OHCT.pdf. Accessed March 31, 2003.

26. "Care of Mouth and Teeth." Pediatric Oncology Center. January 2003. http://www.acor.org/ped-onc/treatment/mouthcare.html#anchor1423829.

27. "Mouth Sores With Cancer." Cincinnati Children's Hospital. November, 1998.http://www.cincinnatichildrens.org/health/info/cancer/home/mouth-sores.htm. Accessed April 4, 2003.

28. Luglie PF et al. "Prevention of periodontopathy and oral mucositis during antineoplastic chemotherapy. Clinical study." Minerva Stomatol 2002 Jun;51(6):231-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12147975&dopt=Abstract.

29. Pitten F et al. "Do cancer patients with chemotherapy-induced leukopenia benefit from an antiseptic chlorhexidine-based oral rinse? A double-blind, block-randomized, controlled study." J Hosp Infect 2003 Apr;53(4):283-291. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12660125&dopt=Abstract.

30. Worthington HV et al. "Interventions for treating oral mucositis for patients with cancer receiving treatment." Cochrane Database Syst Rev 2002;(1):CD001973. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11869616&dopt=Abstract.

31. Levy-Polak MP et al. "Incidence of oral complications and application of a preventive protocol in children with acute leukemia." Spec Care Dentist 1998 Sep-Oct;18(5):189-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10219183&dopt=Abstract.

32. Kaney ML. "Stomatitis." Health Care Professional Version. University of Iowa. http://www.nursing.uiowa.edu/sites/adultpain/genepain/stomatte.htm.

33. Barker B et al. "Oral Management of the Patient With Cancer in the Head and Neck Region." J Calif Dental Assoc 2001 August. http://www.cda.org/member/pubs/journal/jour0801/neckcancer.html.

34. Dodd MJ et al."Radiation-induced mucositis: a randomized clinical trial of micronized sucralfate versus salt & soda mouthwashes." Cancer Invest 2003;21(1):21-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12643006&dopt=Abstract.

35. Dr. John Murren is a medical oncologist specializing in lung cancer at Yale-New Haven Hospital and an associate professor of internal medicine and medical oncology at Yale School of Medicine. Email interview. April 1, 2003.

36. Symonds, Nancy. "Dealing With Mouth Problems." 1998. http://www.learningplaceonline.com/illness/cancer/mouth/problems.htm.

37. Lucas J et al. "Effects of Radiotherapy on the Oral Cavity." OncoLink Treatment Options. November 2001. http://www.oncolink.com/treatment/article.cfm?c=5&s=30&id=17.

38. Porta C et al."Allopurinol mouthwashes in the treatment of 5-fluorouracil-induced stomatitis.
Porta." Am J Clin Oncol 1994 Jun;17(3):246-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8192112&dopt=Abstract.

39. "Oral Complications of Chemotherapy and Head/Neck Radiation." Health Professional Version. National Cancer Institute. August 8, 2002. http://www.nci.nih.gov/cancerinfo/pdq/supportivecare/oralcomplications/healthprofessional/.

40. Larimore W et al. "Diary From a Week in Practice." American Family Physician. February 1, 2000. http://www.aafp.org/afp/20000201/diary.html.

41. Santhanam Suresh, MD, anesthesiologist and co-director of the Pain Management Service at Children's Memorial Hospital in Chicago, IL. Email interview. April 2, 2003.

42. "Vancomycin." Princeton University. http://www.molbio.princeton.edu/courses/mb427/2001/projects/02/vancomycin.htm

43. Redding SW et al. "Treating the discomfort of oral ulceration resulting from cancer chemotherapy." Compend Contin Educ Dent 1999 Apr;20(4):389-92, 394, 396. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11692345&dopt=Abstract .

44. Yamamura K et al."Oral mucosal adhesive film containing local anesthetics: in vitro and clinical evaluation." J Biomed Mater Res 1998 Fall;43(3):313-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9730069&dopt=Abstract.

45. "Recombinant Human GM-CSF." EBioScience. http://www.ebioscience.com/ebioscience/specs/antibody_14/14-8339.htm

46.Granulocyte-Macrophage Colony-Stimulating Factor. http://www.diseasesdatabase.com/sieve/umlsdef.asp?glngUserChoice=5324.

47. Buchsel PC et al. "Granulocyte macrophage colony-stimulating factor: current practice and novel approaches." Clin J Oncol Nurs 2002 Jul-Aug;6(4):198-205. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12087615&dopt=Abstract.

48. Rusthoven J et al. "Use of granulocyte colony-stimulating factor (G-CSF) in patients receiving myelosuppressive chemotherapy for the treatment of cancer." National Guidelines Clearinghouse. April 2000. http://www.guidelines.gov/FRAMESETS/guideline_fs.asp?guideline=000728&sSearch_string=gm%2Dcsf.

49. DeVries A et al. "GM-CSF-mouthwash for treatment of chemoradiation-induced mucositis in patients with advanced head & neck cancer: Primary results of a controlled clinical trial." Annals of Oncology, Vol 11, Suppl.4 October 2000, page 91. http://www.esmo.org/reference/abstracts00/hnc/409.htm.

50. Hejna M et al. "Decrease of duration and symptoms in chemotherapy-induced oral mucositis by topical GM-CSF: results of a prospective randomised trial." Eur J Cancer 2001 Nov;37(16):1994-2002. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11597376&dopt=Abstract.

51. Saarilahti K et al. "Comparison of granulocyte-macrophage colony-stimulating factor and sucralfate mouthwashes in the prevention of radiation-induced mucositis: a double-blind prospective randomized phase III study." Int J Radiat Oncol Biol Phys 2002 Oct 1;54(2):479-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12243825&dopt=Abstract

52. "Mouth Sores." Cancer Treatment Centers of America. http://www.cancercenter.com/aftercareservices/mouthSores.cfm. Accessed April 3, 2003.

53. "Potential Oral Mucositis Treatment Marks Successful Transition into Drug Development." March 4, 2003. http://www.biospace.com/news_story.cfm?StoryID=11882020&full=1.

54. Jeffers M et al. "A Novel Human Growth Factor, FGF-20, Is Active in Animal Models of Inflammatory Bowel Disease." http://ddw02.agora.com/planner/displayabstract.asp?presentationid=3127.

55. Interview with Jonathan Rothberg, CEO, Curagen. The Wall Street Transcript. September 17, 2002. http://www.twst.com/ceos/crgn_sept17.html (Registration required.)

56. "Human Cytokine/Growth Factor/Chemokines Sample Spec Sheets." October 22, 2002. http://www.researchd.com/cytokines/rdi1041.htm.

57. "FDA Grants Fast Track Designation For AES-14 For Oral Mucositis Associated With Breast Cancer Chemotherapy." February 4, 2003. http://www.pslgroup.com/dg/22afa6.htm.

58. MacMillan ML et al. "Fluconazole to prevent yeast infections in bone marrow transplantation patients: a randomized trial of high versus reduced dose, and determination of the value of maintenance therapy." Am J Med 2002 Apr 1;112(5):369-79. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11904111&dopt=Abstract.

59. Dazzi C et al. "Prophylaxis with GM-CSF mouthwashes does not reduce frequency and duration of severe oral mucositis in patients with solid tumors undergoing high-dose chemotherapy with autologous peripheral blood stem cell transplantation rescue: a double blind, randomized, placebo-controlled study." Ann Oncol 2003 Apr;14(4):559-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12649101&dopt=Abstract .

60. Mantovani G. et al. "Phase II clinical trial of local use of GM-CSF for prevention and treatment of chemotherapy- and concomitant chemoradiotherapy-induced severe oral mucositis in advanced head and neck cancer patients: an evaluation of effectiveness, safety and costs." Oncol Rep 2003 Jan-Feb;10(1):197-206. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12469169&dopt=Abstract.

61. Valcarcel D et al."Mouth-washings with recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) do not improve grade III-IV oropharyngeal mucositis (OM) in patients with hematological malignancies undergoing stem cell transplantation. Results of a randomized double-blind placebo-controlled study." Bone Marrow Transplant 2002 May;29(9):783-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12040477&dopt=Abstract.

62. van der Lelie H et al. "Effect of locally applied GM-CSF on oral mucositis after stem cell transplantation: a prospective placebo-controlled double-blind study." Ann Hematol 2001 Mar;80(3):150-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11320899&dopt=Abstract,

63."Long-Term Pain Reduction Delivered by Capsaicin Patch, Phase II Study." April 2, 2003. http://www.ptcommunity.com/Daily/DailyDetail.cfm?chosen=8596 (This is not about mucositis.)

64. "Oral Health in America: A Report of the Surgeon General. Chapter 5." http://www.nidr.nih.gov/sgr/sgrohweb/chap5.htm.

65. "Capsicum." American Cancer Society. http://www.cancer.org/docroot/ETO/content/ETO_5_3X_Capsicum.asp?sitearea=ETO.

66 "Painkilling Candy." Pharmaceutical Achievers. . http://www.chemheritage.org/EducationalServices/pharm/asp/asp52.htm.

67. "Chamomile." American Cancer Society. http://www.cancer.org/docroot/ETO/content/ETO_5_3X_Chamomile.asp?sitearea=ETO.

68. Kathleen Duffy, LPN, medical herbalist and instructor in Chicopee, MA. Telephone interview. April 2, 2003.

69. W. Mark Roberts, MD. Medical Director of Pediatric Hematology and Oncology. Memorial Care Medical Center, Miller Children's Hospital, Long Beach, CA. Email interview. April 4, 2003.

70. Eisen D et al."Clinical utility of oral valacyclovir compared with oral acyclovir for the prevention of herpes simplex virus mucositis following autologous bone marrow transplantation or stem cell rescue therapy." Bone Marrow Transplant 2003 Jan;31(1):51-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12621507&dopt=Abstract.

71. "Standard of Practice : Oral Care for the Research Patient." http://www.cc.nih.gov/nursingnew/nursingresources/Standards%20of%20Practice/ ORALCARESOP9_02.pdf. Access March 31, 2003.

72. El-Sayed S et al. "Prophylaxis of radiation-associated mucositis in conventionally treated patients with head and neck cancer: a double-blind, phase III, randomized, controlled trial evaluating the clinical efficacy of an antimicrobial lozenge using a validated mucositis scoring system." J Clin Oncol 2002 Oct 1;20(19):3956-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12351592&dopt=Abstract.

73. Koc M et al. "Prophylactic treatment of mycotic mucositis in radiotherapy of patients with head and neck cancers." Jpn J Clin Oncol 2003 Feb;33(2):57-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12629054&dopt=Abstract.

74. Lefebvre JL et al. "A comparative study of the efficacy and safety of fluconazole oral suspension and amphotericin B oral suspension in cancer patients with mucositis." Oral Oncol 2002 Jun;38(4):337-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12076696&dopt=Abstract.

75. "Cancer Pain." Cincinnati Children's Hospital. http://www.cincinnatichildrens.org/health/info/pain-mgt/pain/cancer_pain.htm#mucositis. Accessed April 3, 2003.

76. Cerchietti LC et al. "Effect of topical morphine for mucositis-associated pain following concomitant chemoradiotherapy for head and neck carcinoma." Cancer 2002 Nov 15;95(10):2230-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12412178&dopt=Abstract.

77. Krajnik M et al. "Potential uses of topical opioids in palliative care--report of 6 cases." Pain 1999 Mar;80(1-2):121-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10204724&dopt=Abstract.

78. My BMT Journal. http://www.katyhubbell.com/bmtjournal.html. Accessed April 3, 2003.

79. "Homeopathic Remedy Eases Common Side Effect Of Chemotherapy." August 30, 2001. http://www.intelihealth.com/IH/ihtIH/EMIHC000/333/8012/332654.html.

80. Oberbaum M et al. "A randomized, controlled clinical trial of the homeopathic medication TRAUMEEL S in the treatment of chemotherapy-induced stomatitis in children undergoing stem cell transplantation." Cancer 2001 Aug 1;92(3):684-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11505416&dopt=Abstract.

81. Leo Blais, R. PH. Pawtuxet Valley Prescriptions, Coventry, RI. Phone interview. April 4, 2002.

82. "Beta 1,3-Glucan Wound Healing Research." http://www.biopolymer.com/new/woundhealing.pdf. Accessed April 6, 2003.

83. Pediatric Dental Health Topics 25. http://www.angelfire.com/nc/kidsdental/topics25.html Accessed April 7, 2003.

84. "Care of the Mouth and Teeth". Pediatric Oncology Resource Center. http://www.acor.org/diseases/ped-onc/treatment/mouthcare.html#anchor1423829. Accessed April 7, 2003.

85. Miller S et al. "Recent advances in stannous fluoride technology: antibacterial efficacy and mechanism of action towards hypersensitivity." Int Dent J 1994 Feb;44(1 Suppl 1):83-98. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8021041&dopt=Abstract

86. Quilitz R. "Oncology Pharmacotherapy: Modulation of Chemotherapy-Induced Mucositis." Cancer Control Journal. vol2, Sept/Oct 1995. http://www.moffitt.usf.edu/pubs/ccj/v2n5/pharmacotherapy.html.

87 Deborah Markel, certified herbalist, certified natural health professional, and owner of Apothecarian Herbals, LLC in Powhatan, VA. Email interview. April 14, 2002.

88. "Salvia officinalis L.  Lamiaceae." http://www.naturalhealthnotebook.com/Herbs/Latin_Herbs/Genus-S/Salvia_officinalis.htm. Accessed April 7, 2003.

89. Linda Kingsbury, Ph.D. Professional herbalist and herbal consultant. Moscow, ID. http://www.spiritherbs.com. Email interview. April 15, 2003.

90. Karta Purkh Singh Khalsa. Certified naturalist and professional herbalist. Seattle, WA. http://www.kpkhalsa.com/. Email interview. April 15, 2003.

91. Ladas E et al. Coping With Mouth Sores. Herbert Irving Cancer Center. carolann.hs.columbia.edu/services/ patient/fact/mouthsores.pdf. Accessed: April 16, 2003.

92. American Society of Clinical Oncology. "Use of Hematopoietic Colony-Stimulating Factors: Evidence-Based, Practice Guidelines." http://www.asco.org/ac/1,1003,_12-002032-00_18-0011412-00_19-0011414-00_20-002,00.asp?state=. Accessed: April 16, 2003.

93. Paoletti J et al. "Compounding Mouthwashes and Rinses for Oral Mucositis." International Journal Pharmaceutical Compounding. January/February. 1999. www.ijpc.com/_pdf/mouth.pdf

94. Filderman, Elyse. Pharm D, compounding pharmacist at Compounding Pharmacy of Beverly Hills, CA. http://www.compounding-expert.com. Phone interview. April 15, 2003.

95. Bland Diets. NIH Clinical Center. http://www.outputprinting.com/clients/dm/sec1_soft_bland.html. Accessed April 18, 2003.

96. Frank G."Journal Watch." Review of Cerchetti's article (cited in footnote 77). December 10, 2002. http://www.palliative.org/PC/ClinicalInfo/JournalWatch/Miscellaneous.html

97. Research and Clinical Studies on Glutamine. http://www.cambridgenutra.com/professionals/studies.html#Oncology. Accessed April 26, 2003.

98. Glutamine Administration and Doasage Information. http://www.cambridgenutra.com/professionals/administration.html. Accessed April 26, 2003.

99. Cerchietti LC et al. "Effect of topical morphine for mucositis-associated pain following concomitant chemoradiotherapy for head and neck carcinoma." Cancer 2002 Nov 15;95(10):2230-6.

100. Cerchietti LC. Supportive Care Division, Translational Research Unit, Radiotherapy and Radiology Department. Angel H. Roffo Argentine National Cancer Institute. University of Buenos Aires. ArgentinaEmail interview. April 27, 2003.

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