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Mucositis - Chemotherapy Problems and Solutions
Ernest H Rosenbaum, MD, Sol Silverman, MA, DDS, Bernadette Festa, MS, RD, Isadora R. Rosenbaum, MA, Julie Matel, MS, RD, Rosemary Elliott-Snow, RDH, and Robert J. Ignoffo, Pharm D

Chemotherapy
Loss of Appetite (Anorexia)

Abnormalities in Taste Perception
What You Can Do If Foods Taste Too Bitter

What You Can Do If Foods Taste Too Sweet
What You Can Do If Foods Taste Off

What You Can Do In General
Nausea and Vomiting
Anticipatory Nausea and Vomiting
What You Can Do

Medications for Nausea and Vomiting
Sore Mouth and Throat (Mucositis)

Corticosteroid Strategy
What You Can Do If You Have Mucositis

Infections
Antifungal Drugs

Herpes Simplex Virus Treatment
Mucositis Table of Contents


Chemotherapy
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Often, detailed information on nutrition and chemotherapy is not easily available. The specific dietary recommendations in this module show that many drug side effects can be reduced or controlled. Ideally, the physician, nurse or a registered dietitian should be working with the oncologist and yourself.


Loss of Appetite (Anorexia)
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Cancer therapy or the cancer itself may cause changes in your body chemistry that result in a loss of appetite. Pain, nausea, vomiting, diarrhea or a sore or dry mouth may make eating difficult and cause loss of interest in food. It is common to lose your appetite because of anxiety or depression about your disease. Loss of appetite is usually followed by an undesirable loss of weight by taking in an insufficient amount of calories every day.

The reduction of caloric intake can lead to a loss of muscle mass and strength and other complications by causing:

  1. Interruptions of medical therapy, impeding effective cancer therapy
  2. Poor tolerance of surgery
  3. Impaired efficacy of chemotherapy and radiotherapy
  4. Decrease in quality of life
  5. Decrease in immunity

A totally different approach to eating is required when you no longer have an appetite to nourish you. You will need to learn to eat even when you do not feel like eating and to approach eating as an important part of your therapy. Talk to a dietitian, nurse or your doctor about ways to improve your appetite. It is important for your general sense of well-being and your ability to fight the diseases that you eat a nutritious diet and try to maintain your weight.

As appetite may no longer motivate you to eat well, you will now need a planned approach. You may improve your appetite by experimenting with different ways of preparing and serving food. Choose foods high in calories and proteins, so you can get maximum energy and avoid losing weight (which will cause weakness).

If you don't seem to be making progress, you might ask your doctor about medications that can stimulate your appetite such as Megace® or Marinol®, a legally available synthetic form of THC (the active ingredient in marijuana) in capsule form. Marinol® is usually used as an antinausea drug, but it also stimulates the appetite. Some states legally allow marijuana to be used to reduce nausea symptoms for patients receiving chemotherapy under the supervision of their physicians.

Tips for reducing loss of appetite are found under "Helpful Hints for Better Nutrition" in chapter 31, Everyone's Guide to Cancer Therapy (Dollinger, Rosenbaum, Tempero and Mulvihill), or Nutrition Problems: Causes and Solutions chapter 27 Supportive Cancer Care (Rosenbaum and Rosenbaum). Also choose from the high-calorie/high-protein small meal or snack diet ideas in the accompanying booklet on nutrition.


Abnormalities in Taste Perception
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Abnormalities in taste perception is common, especially for those who are receiving concomitant radiation therapy to the neck and mouth area. "Taste blindness," or an altered sense of taste, is a temporary condition that occurs because of effects on taste buds that are mostly located in the tongue. Sometimes, only partial recovery of taste occurs. Common complaints are of food tasting too sweet or too bitter or of a continuous metallic taste.

A loss of taste perception makes it more difficult to eat, which leads to weight loss. Taste loss tends to increase in proportion to the aggressiveness of treatment. With time and healing, the sense of normal taste often returns.

Often a strong aversion to certain tastes or foods follows an illness. Since taste aversions may also be associated with chemotherapy, avoid eating your favorite foods on the day you receive chemotherapy.


What You Can Do If Foods Taste Too Bitter
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  1. Add sweet fruits to meals.
  2. Add honey or sweetener to foods and drinks.
  3. If meat tastes too bitter, eat it cold or at room temperature.
  4. In place of meat, eat blandly prepared chicken and fish, mild cheeses, eggs, dairy products or tofu. All of these foods may taste better when prepared in casseroles or stews.
  5. Marinating foods may make them taste better. Marinate meats or fish in pineapple juice, wine, Italian dressing, lemon juice, soy sauce or sweet-and-sour sauces.
  6. Mouth care can help. Brush your teeth several times a day, and use mouth rinses, water mixed with salt, and/or daily use of Hydrogen peroxide flora or baking soda, or diluted Cepacol® or Chloraseptic®).

What You Can Do If Foods Taste Too Sweet
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  1. Gymnema Sylvestra, a herbal tea that is often used by professional wine tasters, will deaden the taste buds to sweet tastes for about 20 minutes. This should be held in the mouth for about five minutes before eating.
  2. Dilute fruit juice or other sweet drinks with half water or ice.
  3. Avoid sweet fruits; vegetables may be more appealing.

What You Can Do If Foods TasteOff
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  1. Drinking water, tea, ginger ale or fruit juices mixed with club soda may remove some of the strange tastes in your mouth. It might also help to munch on hard candies, such as sugar-free mints of Tic Tacs®. Sugar-free gum or hard candies often reduce after-tastes.
  2. Add wine, beer, mayonnaise, sour cream or yogurt to soups and sauces to disguise the off tastes of other foods.
  3. Eat starchy foods such as bread, potatoes, rice and plain pasta. Do not add butter, margarine or other fatty substances to these foods.
  4. Choose bland foods. Eggs, cheeses (including cottage cheese) hot cereals, puddings, custards, tapioca, cream soups, toast, potatoes, rice and peanut butter are less likely to taste strange than foods with more distinctive flavors.

What You Can Do in General
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  1. Eating in relaxed and pleasant surroundings can help reduce problems of altered or lack of taste (taste blindness).
  2. You may have cravings for spicy and salty foods. Spicy, highly seasoned foods are irritating to many people. However, if your doctor does not advise against such foods, and if you can tolerate them, by all means satisfy such urges.
  3. Often flavorings such as herbs, spices or food seasonings may help. Also, acidic foods such as grapefruit may stimulate taste buds (but avoid them if they irritate your mouth).
  4. Experiment with different food textures such as crunchy, creamy, crispy foods.
  5. High-protein foods and supplements are particularly important when taste blindness prevents you from eating properly.

Nausea and Vomiting
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Nausea and vomiting are frequent side effects of cancer therapy. They can also be brought on by an obstruction in the intestine, irritation of the gastrointestinal tract (gastritis) or brain tumors.

Constant vomiting naturally makes it impossible for you to eat or take fluids, so whatever can be done to reduce nausea should be done before vomiting starts. Paying attention to psychological causes and using antinausea drugs and antianxiety and relaxing medications will help control symptoms. (See for doses of antinausea drugs). Rinsing with 1/4 teaspoon baking soda, 1/4 teaspoon of salt and 1 quart of water can help by neutralizing acids in the mouth

Nausea and vomiting may begin one to three hours after treatment or even as long as two to four days later. You may start to fear therapy, a fear that can gnaw at you and make you want to avoid treatment. Nausea and vomiting may also make problems such as pain control and maintaining an overall good quality of life much harder to deal with. A wide variety of antinausea drugs are available to minimize or prevent the problem.

Medications are available to combat nausea and vomiting. These include Compazine® (prochlorperazine), Ativan®, Benadryl® (diphenhydramine), Decadron®, Dramamine®, Inapsine® (droperidol), Reglan® (metoclopramide), Zofran® (ondansetron) and Kytril® (granisetron). Marinol® is also effective. The FDA has approved Marinol®, the active ingredient in marijuana, in a capsule form. Many patients obtain marijuana from private sources and add it to brownies, cookies or other food, brew it as tea or take it in gelatin capsules by mouth or in rectal suppositories (see below).


Anticipatory Nausea and Vomiting
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Chemotherapy often causes nausea and vomiting. However, it is estimated that up to half of all people receiving chemotherapy experience some nausea or vomiting before treatment. This is known as anticipatory nausea and vomiting (ANV) and usually makes the nausea and vomiting even more severe when the chemotherapy is actually given. ANV can become such a set psychological pattern that the amount of chemotherapy that can be given must be reduced. And once the psychological pattern of ANV is established, it is much harder to control nausea and vomiting before and after treatment. (This behavior pattern was described 90 years ago by the Russian physiologist Pavlov and is referred to today as Pavlov's syndrome.)

The aim in chemotherapy is to deliver a therapeutic amount of drugs with the least side effects. But each chemotherapy agent and each drug combination has a potential for causing nausea and vomiting. Getting three or four drugs at a time, which is often the case, can make the reaction even more severe. The dosage and the number of cycles to be given also contribute to the reaction.

You, your family and even your friends should talk with your doctor about the type of chemotherapy you will be getting. For each drug or drug combination, a program should be established that allows you some control over the situation. With psychological factors playing such a big part, it is very important that you be a participant in preventing nausea and vomiting.

Your anxiety state, how you feel about yourself and your cancer and how you respond to stress and disease, are all important factors in setting up this psychological pattern. And once the pattern is established, all kinds of stimuli can trigger feelings of nausea: the colors or smells in the room where the chemotherapy is given, the smell of rubbing alcohol used to prepare you for the IV needle, the sight of the nurse entering the room or even the sight of the hospital.


What You Can Do
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To deal with this problem, you will have to take steps both to relax before your chemotherapy and to not inadvertently set up situations that become associated with nausea. Some patients benefit from meditation, psychological support and aversion training (through media such as audiotapes to help prevent fear and nausea). Here are some other suggestions.

Medications for Nausea and Vomiting
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Two areas in the brain have been identified as being responsible for nausea and vomiting, and certain drugs and other methods can selectively block these areas. Your doctor can work out a program to combat your nausea, although if one drug or drug combination doesn't work as well as you would both like, you may have to experiment with various programs. Generally, antivomiting drugs (antiemetics) should be taken 30 minutes before chemotherapy so they have time to take effect.

Several antiemetics are available by prescription for use at home in the event that nausea or vomiting are persistent.

Drug Name Usual Dose Side Effects Cost
Prochloperazine
(Compazine®)
10 mg Every 8 hours Sleepiness, dystonic reactions, lockjaw $0.20/tablet
Lorazepam .5-1mg
(Ativan®)
Orally every 4-6 hours as needed 4 to 8 mg Sleepiness, confusion $0.50/tablet
Dolasetron 100mg
(Anzemet®)
Orally one daily Headache, constipation $$
Ondansetron 4-8mg
(Zofran®)
Orally 2 to 3 or tablets daily Constipation $15.00/8 mg
Granisetron 1mg
(Kytril®)
Orally twice a day 2 mg daily Headache $35.00/1mg
Marinol® 5mg Daily 3-4 times or daily as needed Stimulation, confusion $14.00/tablet
Megestrol 800mg Orally divided dose (16 Oz. suspension ) Fluid retention, edema $ 300.00/pint
Megace® 40 mg daily Orally four times Edema, impotence $8.99/tablet
Dexamethasone 2 mg
Decadron®
4-8mg Orally twice daily with meals Insomnia, stomach $0.50/tablet
Metoclopramide 10mg
(Reglan®)
One to two orally four times daily Diarrhea, anxiety, sleepiness $0.60/tablet

Delayed nausea and vomiting can occur after cisplatin, carboplatin, and cyclophosphamide chemotherapy. The most effective antinausea medications for delayed nausea and vomiting are Reglan® and dexamethasone. However,these drugs have more side effects than the "setrons" (ondansetron,granisetron, and dolasetron). A setron should be used after Reglan® and dexamethasone has been tried. If effective a setron may be used as a preventive therapy during the next cycle of chemotherapy.


Sore Mouth and Throat (Mucositis)
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A sore or ulcerated mouth or throat is a frequent side effect of chemotherapy. This condition may clear up in a few days, unless your recovery is slowed by malnutrition If symptoms persist, consult your physician; you may have a viral or fungal infection.

The mouth and digestive tract are composed of cells (mucosa) that are more sensitive to chemotherapy. The lining, or mucosa, of the gastrointestinal tract, which includes the inside of the mouth and throat, is one of the most sensitive areas of the body. Thus, during or after chemotherapy, a cancer patient may present with mouth problems, ranging from dryness to ulcers. Many chemotherapy drugs can inflame the lining, a condition called mucositis. Mucositis appears as redness (inflammation), sores (ulcerations) and associated discomfort and pain.

These mouth problems are most often due to chemotherapy but can be caused by other medication. Three to ten days following chemotherapy, patients may experience a burning sensation, followed by ulcers. When ulceration develops, treatment is mostly supportive until the cells regenerate themselves, which takes about 7 to 14 days (most commonly associated with a low white blood cell count). This can impact on oral comfort and nutrition, but adequate care can minimize these effects. Since these changes (mucositis) are primarily inflammatory, corticosteroid treatment is often helpful.


Corticosteroid Strategy
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Systemic: high dose/short course
Prednisone 40-80 mg daily orally in one dose
Less than 2 weeks, no taper

Topical: potent corticosteroids (gel & ointment)* Fluocinonide (Lidex®) 0.05%
Clobetasol (Temovate®) 0.05%
Halobetasol (Ultravate®) 0.05% *Paste: mix ointment with equal parts Orabase B®

Mouth Rinse: elixir dexamethasone 0.5 mg/5ml
1 tsp 3 times daily; hold 1 minute, then spit out


Oral Hygiene
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When using cytotoxic chemotherapeutic drugs, it is extremely important to keep patients free from the oral foci of infection and pain to minimize local infection and bacteremia, and to enable them to maintain a nutritious diet. The chemotherapeutic agents utilized to eradicate tumor production also adversely affect normal cells, particularly those that have relatively high turnover rates, such as oral epithelial tissues. The depressant effect of therapy on oral epithelial mitoses can result in thinning and ulceration of the tissues as well as salivary glands and taste dysfunctions. The oral ulcerations may be due to direct cellular cytotoxicity from the chemotherapeutic agents, increased susceptibility to microorganisms owing to neutropenia (bone marrow suppression), trauma, or a combination of these factors.

A good oral hygiene program includes dental cleaning and scaling, followed by daily brushing and careful flossing to reduce plaque.

Any scaling, cleaning, tooth extractions or repair of cavities should be done before cancer therapy begins. Extractions especially should be completed at least two weeks before therapy to give your mouth a chance to heal. Ill-fitting dentures should be adjusted or replaced. Any periodontal or dental work has to be coordinated with your oncologist.

Before any dental work is to be performed, your blood counts should be checked to be sure that your body can take care of any infection or bleeding (low white cell counts can lead to infections, and a low platelet count may lead to bleeding). Antibiotics are recommended if your white blood cell count is low or there is an infection. Unless there is an emergency, dental procedures should be delayed till the blood counts return to a normal range.

Patients should brush their teeth 3 to 4 times a day with a soft toothbrush or sponge and use floss with care so as not to cut or injure the gums.

Patients should rinse their mouths frequently with salt water, baking soda or chlorhexidine (Peridex® or Periogard®) following chemotherapy. The use of floss, electric toothbrushes and Waterpic® appliances should be curtailed if the gums are swollen, sore or tend to bleed.

Xylocaine® is a local anesthetic available as a 2% gel used topically to decrease pain, but has a short duration of action. Over-the-counter (OTC) Orabase B® may also be of some help. Protective agents such as SucralfateTM or Kaopectate® are also used to cover ulcers and decrease irritation. Irritant substances like hydrogen peroxide may worsen the ulcers. Topical steroids should be used with caution as they may facilitate fungal infections. In addition, patients should avoid foods that cause irritation. Preference should be put on soft moist foods.

The following daily steps will help your mouth stay in good shape:

  1. Use a soft-bristle toothbrush and soften it more by soaking it in warm water. You may find that brushing with a paste of baking soda and water is less irritating than commercial toothpaste. Biotene toothpaste (OTC) is also non-irritating and contains natural salivary enzymes that help control bacteria.
  2. If brushing your teeth is painful, use either a cotton swab or Toothetes, a sponge-tip stick impregnated with a dentifrice (toothpaste). A Q-tip dipped in 3% hydrogen peroxide followed by a warm water rinse may help remove debris from around the teeth.
  3. Avoid commercial mouthwashes. Some of these have ingredients (especially alcohol) that can irritate your mouth even more. Lemon glycerin swabs may make your mouth feel clean but they are not recommended because glycerin can dehydrate and will make your mouth drier.
  4. A Water-Pik® to cleanse your mouth is helpful but must be used with caution, since the pressure of the waterjet may irritate tissue.
  5. Undiluted clorhexidine mouth rinses (Peridex ®, Periogard®) may help gum inflammation and bleeding, but contain alcohol and may sting. Dilution of these rinses defeats the antibacterial advantages.

What You Can Do If You Have Mucositis
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In chemotherapy, the mucositis is usually due to the low white blood cell count; in radiation to the head and neck, it is usually due to the necrotic and inflammatory effect of radiation energy on oral mucosa.

If the soreness in your mouth becomes severe, there are quite a few anesthetic agents you can use on a short-term basis. If your symptoms persist, you should have a complete mouth evaluation. There is an increased risk of mucositis for those who smoke.


Infections
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Mouth infections can be dangerous. Examine your mouth every day for any irritation or abnormal appearances or feelings. Report any changes to your doctor. If you do get an infection, it should be treated promptly. Sometimes the diagnosis can be made by clinical characteristics, but may require a smear or cultures.

  1. If you have a herpes virus/infection-acute or recurrent-your doctor may prescribe oral Acyclovir® tablets. Treatment is also supportive: bland mouth rinses, analgesics, liquids to avoid dehydration, and calories to minimize weight loss and susceptibility to other infections and/or debilitation.
  2. Monilia (thrush Candidiasis) requires antifungal agents, such as Mycostatin ® (nystatin) oral suspension, Mycelex ® (clotrimazole) troches, Nizoral® (ketoconazole) tablets, Diflucan® (fluconazole) tablets, oral solution, Fungizone ®(amphotericin) oral solution.
  3. You can freeze nystatin liquid in medicine cups or ice cube trays and let it melt in your mouth.

Antifungal Drugs
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Systemic
Ketoconazole ® (Nizoral) tabs, 200-400 mg/day Metabolized in liver; to take with food
Fluconazole ® (Diflucan) tabs, 100-200 mg/day Metabolized in kidneys; food elective; saliva level

Topical (dissolve, swish, swallow)
Clotrimazole (Mycelex ®) oral troches, 10 mg 5/day vaginal troches, 100-200 mg 1-2/day
Nystatin (Mycostatin ®) suspension, 500,000 u 3/day pastille, 200,000 u 2-3/day vaginal troches, 100,000 u 3-5/day powder, 100,000 u/gm (dentures)
Mycolog ® cream (angular cheilitis) Amphotericin suspension (Fungizone ®) 1 ml (100 mg) 4xd


Herpes Simplex Virus Treatment
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Systemic:
Acyclovir (Zovirax ®) ............400 mg 3/day
Famciclovir (Famvir ®) ............125 mg 2/day
Valacyclovir (Valtrex ®) ............500 mg 2/day
Foscarnet (Foscavir ®) ............60 mg/kg every 8 hours




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