Chemotherapy-Induced Oral Mucositis Medication

Oral mucositis (OM) is a self-limited condition. Currently, no approved preventive or therapeutic agent consistently prevents oral mucositis in all clinical settings.

Palifermin, or human recombinant keratinocyte growth factor (KGF), given intravenously significantly reduces 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, with autologous or allogeneic stem cell transplantation.^{[3, 10]}

Palifermin has also demonstrated efficacy in a phase II study of patients with metastatic colorectal cancer undergoing treatment with fluorouracil-based chemotherapy. However, a phase II study of palifermin in patients with advanced head and neck cancer being treated with combined chemoradiation therapy did not demonstrate statistically significant differences between palifermin and placebo groups.

In a randomized trial, a single dose of palifermin before each chemotherapy cycle significantly reduced the cumulative incidence of moderate-to-severe mucositis. Except for thickening of oral mucosa, palifermin was well tolerated.^[11] Additional studies evaluating palifermin are ongoing.

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 the prevention and/or treatment of oral mucositis in the future. A selection of related clinical trials is as follows:

• Study of Epidermal Growth Factor on Oral Mucositis Induced by Intensive Chemotherapy for Hematologic Malignancies
• Dose Ranging Study to Assess the Safety and Efficacy of SCV-07 for the Delay to Onset of Severe Oral Mucositis in Patients Receiving Chemoradiation Therapy for Head and Neck Cancer
• A Phase II Controlled Trial of Velafermin for Prevention of Oral Mucositis
• Efficacy of SNX-1012 in the Treatment of Oral Mucositis
• A Study of Palifermin for the Reduction of Oral Mucositis in Subjects With Advanced Head and Neck Cancer

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, interleukin [IL]–1, IL-11, transforming growth factor [TGF]–beta3), amino acid supplementation (eg, glutamine), vitamins, topical morphine, colony-stimulating factors, cryotherapy, and laser therapy. Low-level laser therapy has demonstrated evidence of efficacy; however, regimens, including laser wavelength and intensity, have varied considerably from study to study and specialized equipment is required.

Class Summary

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.

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.

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.

Class Summary

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.

Class Summary

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.

Class Summary

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 oral mucositis 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.

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.

Famciclovir (Famvir)

For prophylactic use to prevent recurrent HSV infections. Prodrug, which, when biotransformed into active metabolite, penciclovir, may inhibit viral DNA synthesis/replication. Inhibits viral DNA polymerase.

Class Summary

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.

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.

Class Summary

Human KGF may be considered for hematologic malignancies.^[12]

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 oral mucositis incidence and duration in patients with hematologic malignancies.