eMedicine Specialties > Dermatology > Diseases of the Oral Mucosa
Chemotherapy-Induced Oral Mucositis: Treatment & Medication
Updated: Oct 31, 2008
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Medical Care
Because oral mucositis (OM) is self-limited, management of lesions is divided into 5 main approaches, including the following:
- Oral debridement: Because patients with oral mucositis lesions are neutropenic and thrombocytopenic, perform oral debridement with caution because toothbrushing can cause gingival bleeding and, more importantly, result in transient bacteremia. In some centers, sponge-tipped applicators and gauze soaked in sodium chloride solution are used for oral debridement because of these concerns. Dried secretions may become caked on the mucosal surfaces, particularly the palate. Mucolytic agents, such as Alkalol, help to soften and dislodge them.
- Oral decontamination (mouth care): This regimen consists of antifungal and antibacterial rinses. The fluoride rinses and gels used in some oral care regimens are used primarily for antibacterial activity against gingival plaque; they are not used expressly for the prevention of dental caries. Candidal prophylaxis usually includes nystatin rinses and clotrimazole troches. If patients have a very dry mouth, troches are not as effective because they do not dissolve well in a dry environment. Amphotericin rinses also are occasionally used in place of nystatin. Fluconazole may be used for candidal prophylaxis or for treatment of suspected candidiasis.
- Topical and systemic pain management: Pain in patients with oral mucositis may be severe and not just limited to the oral mucosa. Local rinses (eg, 2% viscous lidocaine) and systemic analgesics are used together to control pain. Frequent rinsing with sodium chloride solution helps to keep the mucosa moist, reduces caking of secretions, and soothes inflamed/ulcerated mucosa.
- Prophylaxis: Systemic prophylaxis for oral mucositis is generally limited to antivirals; however, some centers use fluconazole as prophylaxis against candidiasis.
- Control of bleeding: Maintaining platelets at 20,000 cells/µL and using topical thrombin packs and topical antifibrinolytic agents, such as tranexamic acid, may control bleeding from ulcers.
- Comprehensive, evidence-based guidelines for the prevention and treatment of oral mucositis was published in 2007.4
Consultations
Involving dentists and oral medicine specialists in the care of a patient with oral mucositis is important because oral hygiene modifies the occurrence and the severity of oral mucositis and alpha-hemolytic streptococcal sepsis has become increasingly prevalent (in patients undergoing HCT).
- In the outpatient setting, a dentist or an oral medicine specialist should see patients several weeks or months prior to the initiation of chemotherapy, especially in the case of HCT. If this is not possible, the patient should be seen for an evaluation during his or her hospitalization for a baseline dental evaluation, even if intervention may not be possible at that visit.
- The role of the dentist/oral medicine specialist is to identify and remove dental/oral sources of infection prior to myelosuppression and HCT.
- Procedures may include but are not limited to comprehensive oral and head and neck examination, full mouth series of dental radiographs, and pulp-vitality testing.
- Appropriate therapy includes identification and management of soft tissue lesions, restoration of carious teeth, extraction of nonsalvageable teeth, extraction of third molars as necessary (particularly those that are not full bony impacted and not fully erupted), and scaling and root planing. Treatment should be completed at least 1 week before initiation of conditioning therapy for HCT.
- After the patient has been admitted to the hospital, the dentist/oral medicine specialist should follow up with these patients to monitor oral mucositis, identify signs and symptoms of secondary infection, evaluate slow healing of oral mucositis, identify non-oral mucositis oral mucosal pathology, and adjust the oral care regimen as needed.
Diet
A bland, soft diet is recommended. Patients should keep the mouth moist with frequent sips of water, ice chips, or popsicles. Patients with severe oral mucositis may require total parenteral nutrition. Patients should avoid acidic, spicy, salty, coarse, and dry foods.
Activity
Patients with chemotherapy-induced oral mucositis are generally seen in the hospital. Activities are prescribed for them as part of the daily physical therapy regimen.
Medication
Oral mucositis (OM) is a self-limited condition. Currently, no approved preventive or therapeutic agent consistently prevents oral mucositis in all clinical settings. Human recombinant keratinocyte growth factor (KGF) given intravenously was recently demonstrated to significantly reduce the incidence, duration, and severity of oral mucositis in patients undergoing autologous HCT and has been approved for use in patients with hematologic malignancies undergoing high-dose chemotherapy with or without concomitant total body irradiation. More studies of KGF in other patient populations are ongoing to evaluate safety and efficacy, especially in patients with solid cancers that are known to express growth factor receptors because tumor growth promotion is a concern. Other biological-based treatments are currently in clinical trials, and it is not unreasonable to expect a number of these agents to be approved for treatment of oral mucositis in the future.
Medications are used for prophylaxis against viral and fungal infections, decontamination of the oral cavity, and palliation for pain. This section discusses common medications used for prophylaxis, decontamination, and topical palliation only. Topical palliation for pain may be as simple as frequent sodium chloride solution or salt/bicarbonate of soda rinses and ice chips. Often, 2% viscous lidocaine is mixed in equal volumes with diphenhydramine hydrochloride and bismuth subsalicylate (Kaopectate) or even aluminum hydroxide/magnesium hydroxide (Maalox) as a soothing mouth rinse. In general, most patients require systemic pain control using centrally acting narcotic agents.
Experimental therapies that have been reported include the use of topically applied agents, such as misoprostol (a cytoprotectant), cytokines, and other modifiers of inflammation (eg, IL-1, IL-11, TGF-beta3), amino acid supplementation (eg, glutamine), vitamins, topical morphine, colony-stimulating factors, cryotherapy, and laser therapy.
Antifungals
These agents are used prophylactically against candidal infections in all patients.
Nystatin (Nystex, Mycostatin, Nilstat)
Fungicidal and fungistatic antibiotic obtained from Streptomyces noursei. Effective against various yeasts and yeastlike fungi. Changes permeability of fungal cell membrane after binding to cell membrane sterols, causing cellular contents to leak. Continue treatment until 48 h after disappearance of symptoms. Not absorbed significantly from GI tract.
Adult
500,000 U swish and swallow 4-5 times/d
Pediatric
Administer as in adults
None reported
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Do not use to treat systemic mycoses; Stevens-Johnson syndrome has rarely been reported; more common but less severe associated adverse effects include nausea, vomiting, diarrhea, and local irritation
Clotrimazole (Lotrimin, Mycelex, Femazole)
Broad-spectrum antifungal agent that inhibits yeast growth by altering cell membrane permeability, causing death of fungal cells. Reevaluate diagnosis if no clinical improvement after 4 wk.
Adult
10 mg troche may be dissolved 3 times/d for 7-10 d or for duration of chemotherapy
Pediatric
Children: Not established
Adolescents: Administer as in adults
None reported
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Not for treatment of systemic fungal infections; avoid contact with the eyes; if irritation or sensitivity develops, discontinue use and institute appropriate therapy
Fluconazole (Diflucan)
Fungistatic activity. Synthetic oral antifungal (broad-spectrum bistriazole) that selectively inhibits fungal cytochrome P-450 and sterol C-14 alpha-demethylation, which prevents conversion of lanosterol to ergosterol, thereby disrupting cellular membranes.
Adult
100-200 mg for 3-10 d depending on severity of infection
Pediatric
3-6 mg/kg PO qd for 14-28 d or 6-12 mg/kg PO qd depending on severity of infection
Levels may increase with hydrochlorothiazides; levels may decrease with long-term coadministration of rifampin; coadministration may decrease phenytoin clearance; may increase concentrations of theophylline, tolbutamide, glyburide, and glipizide; effects of anticoagulants may increase with coadministration; cyclosporine concentrations may increase when administered concurrently
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Adjust dose for renal insufficiency; monitor closely if rash develops, and discontinue drug if lesions progress; may cause clinical hepatitis, cholestasis, and fulminant hepatic failure (including death), with underlying medical conditions (eg, AIDS, malignancy) and while taking multiple concomitant medications; not recommended in breastfeeding
Antibacterials
Rinses are the basis of the oral decontamination regimen.
Chlorhexidine gluconate (Peridex, PerioGard)
Effective, safe, and reliable antiseptic mouthwash. A polybiguanide with bactericidal activity; usually supplied as gluconate salt. At physiologic pH, salt dissociates to a cation that binds to bacterial cell walls. Active against gram-positive and gram-negative organisms, facultative anaerobes, aerobes, and yeast. Precede use of solution by flossing and brushing teeth, if possible. Completely rinse toothpaste from mouth.
Adult
Swish 15 mL undiluted oral rinse around mouth for 30 seconds, then expectorate; caution patient not to swallow medication; do not ingest food for 2-3 h following treatment
Pediatric
Not established; suggested as in adults
None reported
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Staining of oral surfaces, tooth restorations, and dorsum of tongue may occur; keep out of eyes and ears; for topical use only; case reports of anaphylaxis exist following chlorhexidine disinfection; because of drug interactions, do not use within 30 min of nystatin rinse
Anesthetics
Oral rinses are used to reduce pain and discomfort.
Viscous lidocaine 2% (Xylocaine, Dilocaine, Anestacon)
Decreases permeability to sodium ions in neuronal membranes. Results in inhibition of depolarization, blocking transmission of nerve impulses.
Adult
5 mL swish and expectorate
Pediatric
Apply to affected area prn
None reported
Documented hypersensitivity; avoid use in Adams-Stokes syndrome and Wolf-Parkinson-White syndrome
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
For external or mucous membrane use only; do not use in eyes
Antivirals
Nucleoside analogs are initially phosphorylated by viral thymidine kinase to eventually form a nucleoside triphosphate. These molecules inhibit HSV polymerase with 30-50 times the potency of human alpha-DNA polymerase.
Acyclovir (Zovirax)
For patients who have been exposed to HSV or VZV infection. Reactivation of such infections occurs in 70-90% of patients who have antibodies to these agents and can aggravate preexisting OM and result in systemic infection. Inhibits activity of HSV-1 and HSV-2. Has affinity for viral thymidine kinase, and, once phosphorylated, it causes DNA chain termination when acted on by DNA polymerase. Patients experience less pain and faster resolution of cutaneous lesions when used within 48 h from rash onset. May prevent recurrent outbreaks. Early initiation of therapy is imperative.
Adult
400 mg PO tid
Pediatric
5 mg/kg/dose IV q8h or 750 mg/m2/d divided q8h
Concomitant use of probenecid or zidovudine prolongs half-life and increases CNS toxicity
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Caution in renal failure or when using nephrotoxic drugs
Valacyclovir (Valtrex)
Prodrug and is rapidly converted to the active drug acyclovir. More expensive but has better bioavailability and a more convenient dosing regimen than acyclovir.
Adult
First episode herpes simplex: 1 g bid for 10 d, preferably beginning within 48 h of onset
Recurrent episode herpes simplex: 500 mg bid for 5 d beginning within 24 h of onset
Suppressive dosing for HSV: 500 mg to 1 g/d
Pediatric
Not established
Probenecid, zidovudine, or cimetidine coadministration prolongs half-life and increases CNS toxicity of valacyclovir
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Caution in renal failure (decrease dose) and coadministration of nephrotoxic drugs; associated with onset of hemolytic uremic syndrome
Famciclovir (Famvir)
For prophylactic use to prevent recurrent HSV infections. Prodrug that, when biotransformed into active metabolite, penciclovir, may inhibit viral DNA synthesis/replication. Inhibits viral DNA polymerase.
Adult
Prophylaxis: 500-1000 mg PO bid for up to 1 y
Pediatric
Not established
Coadministration of probenecid or cimetidine may increase toxicity; coadministration increases bioavailability of digoxin
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Caution in renal failure or coadministration of nephrotoxic drugs
Gastrointestinal agents
These agents are used to protect the GI tract from irritants.
Sucralfate (Carafate)
Forms viscous adhesive substance that protects oral and GI lining against pepsin, peptic acid, bile salts, and other irritants. Use susp.
Adult
1 g PO qid
Pediatric
Not established
When swallowed (if used for duodenal ulcers), may decrease effects of ketoconazole, ciprofloxacin, tetracycline, phenytoin, warfarin, quinidine, theophylline, and norfloxacin
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Caution in renal failure and conditions that impair excretion of absorbed aluminum (when swallowed)
Gelclair Bioadherent Oral Gel
Adheres to mucosal surface of mouth and forms protective coating that shields exposed and overstimulated nerve endings. Ingredients include polyvinylpyrrolidone, hyaluronic acid, glycyrrhetinic acid, and water.
Adult
Prepare single-dose packet; rinse and gargle for 1 min then spit out
Pediatric
Administer as in adults
None
None
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
None
Growth factors
Human KGF may be considered for hematologic malignancies.5
Palifermin (Kepivance)
Human KGF that enhances epithelial cell proliferation, differentiation, and migration. KGF receptor not present on hematopoietic cells, but has enhanced growth of human epithelial tumor cell lines in vitro. Indicated to decrease severe OM incidence and duration in patients with hematologic malignancies.
Adult
60 mcg/kg/d IV for 3 consecutive days before and 3 consecutive days after myelotoxic therapy for a total of 6 doses
Pediatric
Not established
Data limited; binds to heparin in vitro (if heparin used to maintain an IV line, rinse line with 0.9% NaCl before and after administration)
Documented hypersensitivity to Escherichia coli –derived proteins, palifermin, or other product components
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Safety has not been established with nonhematologic malignancies; common adverse effects include skin toxicities (eg, rash, erythema, edema, pruritus), oral toxicities (eg, tongue discoloration, tongue thickening, dysgeusia), pain arthralgias, and dysesthesia; potential for immunogenicity (antibodies to palifermin), as with other proteins; do not filter; protect from light
More on Chemotherapy-Induced Oral Mucositis |
| Overview: Chemotherapy-Induced Oral Mucositis |
| Differential Diagnoses & Workup: Chemotherapy-Induced Oral Mucositis |
 Treatment & Medication: Chemotherapy-Induced Oral Mucositis |
| Follow-up: Chemotherapy-Induced Oral Mucositis |
| Multimedia: Chemotherapy-Induced Oral Mucositis |
| References |
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References
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Further Reading
Keywords
oral mucositis, OM, hairy tongue, chemotherapy complications, ulceration of the oral mucosa, ulcers in the mouth, alpha-hemolytic streptococcal infection, viridans streptococci, septicemia, leukoedema, atrophy of the mucosa, chemotherapy-related oral ulcers, ulcerative OM, ulcerative oral mucositis, HSV infection
