Mucositis is a common complication of cytotoxic chemotherapy. The incidence of mucositis in patients receiving cytotoxic chemotherapy for solid tumors is estimated at 5% to 40%.1 The terms mucositis and stomatitis have been used interchangeably in medical and nursing literature but are not synonymous. Mucositis refers to the inflammatory process involving the mucous membranes of the oral cavity and the gastrointestinal tract. Stomatitis refers to inflammatory diseases of the mouth including not only the mucosa, but also dentition, periapices, and periodontium. Stomatotoxic or mucotoxic refers to agents or procedures capable of causing injury to the mucosa, as in stomatotoxic chemotherapy.2
Historically, oral mucositis (OM) has been thought to result from damage to the epithelium by chemotherapy or radiation therapy. Chemotherapy agents target nonspecific proliferative tumor cells, but they cannot differentiate between tumor cells and rapidly dividing normal cells. Ultimately, basal cells are injured and die, with no new cells to replace the damaged cells, leading to a thinning and atrophic mucosa, with ulceration development.3
Sonis et al³have created a pathobiologic model for the development and resolution of mucositis, which involves 5 phases:
- Upregulation and message generation
- Amplification and signaling
Courtesy of Stephen T. Sonis, DMD, DMSc, Harvard’s Brigham and Women’s Hospital. Reproduced with permission.
The initiation phase includes the generation of reactive oxygen species (ROS) caused by chemotherapy or irradiation, which leads to biologic events and subsequent mucosal injury. Upregulation and message generation result from the activation of transcription factors by both radiation therapy and chemotherapy. Once activated, these factors control the synthesis of proteins (cytokines), which target specific tissue, resulting in further tissue damage. During the signaling and amplification phase, there is direct damage to the cells by the cytokines, with tumor necrosis factor a (TNF-a) activation, creating a feedback loop that leads to additional proinflammatory changes. Damage here occurs beneath the mucosal surface. Ulceration is most clinically evident, extending from the epithelium to the submucosa, with exposure ofneuron endings leading to pain. The ulcerated region undergoes colonization that penetrates into surrounding tissue, leading to stimulation of proinflammatory cytokines. In the healing phase, the surface of the ulcer becomes covered with epithelium, leading to layering of cells and establishment of normal healthy mucosa.1, 3, 4
Early identification of patients at risk for mucositis is critical. Preventive measures and management strategies may be incorporated into the treatment plan. Risk factors have been classified into 2 categories3-5: patient related and treatment related.
- Patient-related risk factors
- Age (very young, due to increased cell turnover rate, and elderly, due to delayed healing)
- Sex (data suggest that women receiving fluorouracil [5-FU]-based therapy may be at higher risk)6
- Previous cancer treatment
- Abnormal renal function
- Poor oral hygiene
- Low body mass index
- Decreased saliva production (xerostomia)
- Production of high levels of cytokines involved in immune mediation (may increase risk of OM)7
- Treatment-related risk factors
- Specific chemotherapy agents (eg, antimetabolites, antitumor antibiotics, alkylating agents)
- Dose of chemotherapy agents and schedule
- Combined modality: radiation plus chemotherapy carries greater risk
Effect of OM on Patient Outcomes
Patients often state that OM is one of the most distressing side effects of chemotherapy. Chen8 studied 57 patients in an ambulatory chemotherapy unit and found that 75.4% had experienced at least 1 episode of OM since their first chemotherapy infusion. Dry lips were the most common symptom, and pain on swallowing was considered the most distressing OM-related effect.8
OM is uncomfortable and distressing, and can lead to treatment delays or discontinuation. Severe OM can have additional serious effects. Grade 3/4 oral mucositis is associated with3,9
- 3-fold increase in risk of infection and infection-related death during myelosuppression
- 10-fold increase in utilization of total parenteral nutrition (TPN) and fluids
- 10-fold increase in use of opioid analgesics
- Additional 7 days of hospitalization per episode
- Incremental cost of = $3,500 per episode
Accurate oral assessment is critical in the prevention and management of OM. A number of grading and assessment tools are available for assessing the oral cavity:
- The Oral Assessment Guide (OAG)5 focuses on changes in the oral cavity related to cancer treatment, including function and tissue assessment
- The following tools assess the amount of tissue involved but do not include function:
- Oral Mucosa Rating Scale (OMRS)
- Oral Mucositis Index (OMI)
- Oral Mucositis Assessment Scale (OMAS)5
Additional information on these assessment tools to measure oncology nursing–sensitive outcomes may be accessed at:http://onsopcontent.ons.org/toolkits/evidence/Clinical/pdf/MucositisTools.pdf. Accessed January 27, 2010.
Additionally, there are tools available for grading OM, such as the National Cancer Institute Common Toxicity Criteria (NCI CTC v.3) used by the World Health Organization: CTCAEv4.02.pdf. In version 4.02, mucositis is listed under GI Events page 18. http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.02_2009-09-15_QuickReference_8.5x11.pdf Accessed February 18, 2010.
Prevention and Treatment
Most preventive and treatment strategies for OM are based on limited, anecdotal clinical data. Good oral hygiene and comprehensive patient education form the basic components of OM preventive interventions.10 Evidence-based information on the ONS PEP® card11 recommends initiation and maintenance of oral hygiene protocols. These should involve multidisciplinary teams including dentists, frequent oral assessments, and patient teaching on oral care. Patients should
- Brush twice a day, for at least 90 seconds, with a soft toothbrush, allowing brush to dry completely
- Floss at least once a day, using caution if platelets are low
- Rinse 4 times a day with a bland rinse (normal saline, sodium bicarbonate, or a mixture)
- Avoid tobacco, alcohol, and irritating foods
- Use moisturizers to protect lips (water based)
- Maintain adequate hydration
Nonpharmacologic approaches for prevention include oral cryotherapy for patients receiving chemotherapy with bolus 5-FU.12-14 Patients undergoing bolus 5-FU therapy should hold ice or ice-cold water in their mouths for 5 minutes prior to infusion, during infusion, and for 30 minutes after completion of infusion.11 Oral cryotherapy should not be used for patients undergoing continuous 5-FU therapy in combination with oxaliplatin because of the risk of oropharyngeal paresthesia (cold-induced neuropathy) associated with oxaliplatin therapy.12 Treatment of established OM remains a challenge and currently focuses on palliative management.13
The Multinational Association of Supportive Care in Cancer (MASCC)14 in conjunction with the International Society of Oral Oncology developed guidelines for the evaluation, prevention, and treatment of OM. The 2005 MASCC guidelines have been revised and can be accessed at http://www.mascc.org/mc/page.do?sitePageId=88037. Accessed January 27, 2010.
Patient Care Management Resources
The Oncology Nursing Society (ONS) has published an evidence-based practice quick reference card (ONS PEP®Card) on the management of OM. The ONS resource card can be accessed at http://www.ons.org/Research/PEP/Topics/Mucositis. Accessed January 27, 2010
- Peterson D. New strategies for management of oral mucositis in cancer patients. J Support Oncol. 2006;4(2 suppl 1):9-13.
- National Cancer Institute (NCI). Oral complications of chemotherapy and head/neck radiation (PDQ). 2008.http://www.cancer.gov/cancertopics/pdq/supportivecare/oralcomplications/healthprofessional. Updated October 6, 2009. Accessed January 27, 2010.
- Sonis ST. Pathobiology of mucositis. Semin Oncol Nurs. 2004;20:11-15.
- Cawley MM, Benson LM. Current trends in managing oral mucositis. Clin J Oncol Nurs. 2005;9:584-592.
- Eilers J, Million R. Prevention and management of oral mucositis in patients with cancer. Semin Oncol Nurs. 2007;23:201-212.
- Sloan JA, Goldberg RM, Sargent DJ, et al. Women experience greater toxicity with fluorouracil-based chemotherapy for colorectal cancer. J Clin Oncol. 2002;20:1491-1498.
- Sonis ST, Fey EG. Oral complications of cancer therapy. Oncology [Williston Park], 2002;16:680-686.
- Chen H-M. Patients’ experiences and perceptions of chemotherapy-induced oral mucositis in a day unit. Cancer Nurs. 2008;31:363-369.
- Elting LS, Cooksley C, Chambers M, et al. The burdens of cancer therapy: clinical and economic outcomes of chemotherapy-induced mucositis. Cancer. 2003;98: 1531-1539.
- McGuire DB, Correa MEP, Johnson J, Wienandts P. The role of basic oral care and good clinical practice principles in the management of oral mucositis.Support Care Cancer. 2006;14:541-547.
- Oncology Nursing Society. Mucositis PEP® Card. 2008. http://www.ons.org/Research/PEP/Topics/Mucositis. Accessed January 27, 2010.
- Migliorati CA, Oberle-Edwards L, Schubert M. The role of alternative and natural agents, cryotherapy, and or laser for management of alimentary mucositis.Support Care Cancer. 2006;14:533-540.
- Saadeh CE. Chemotherapy- and radiotherapy-induced oral mucositis: review of preventive strategies and treatment. Pharmacotherapy. 2005;25:540-554.
- Multinational Association of Supportive Care in Cancer (MASCC)—International Society for Oral Oncology (ISOO). MASCC/ISOO Summary Guidelines Table. 2006. http://www.mascc.org/mc/page.do?sitePageId=88037. Accessed January 27, 2010.
atrophic-wasting away or diminution
cytotoxic-chemicals directly toxic to cells, preventing their reproduction or growth. Cytotoxic therapies kill cells outright, as opposed to cytostatic therapies, which only suppress or inhibit growth
cytokines-a small protein released by cells that have specific effects on the interactions between cells, on communication between cells, or on the behavior of cells
dentition-type, number, and arrangement of a set of teeth
epithelium-membranous tissue composed of one or more layers of cells separated by very little intercellular substance and forming most internal and external surfaces of the body and its organs
neuron-any of the impulse-conducting cells that constitute the brain, spinal column, and nerves
periapices-area surrounding of the bottom of the root of a tooth
periodontium-specialized tissues that surround and support the teeth, maintaining them in the maxillary and mandibular bones
proliferative-rapidly growing and increasing in number
tumor necrosis factor a (TNF-a)-serum glycoprotein produced by activated macrophages and other mammalian mononuclear leukocytes
transcription factors-proteins that bind to DNA and regulate gene expression
xerostomia-decreased flow of saliva. May be due to aging, disease, treatment, or medication
Jennifer Hester, DNP, RN, AOCNS®, ACHPN, Oncology/Palliative Care Clinical Nurse Specialist, Health Alliance-University Hospital and Barrett Cancer Center, Cincinnati, OH. This study was funded by the J. Patrick Barnes Grant for Nursing Research of the DAISY Foundation.
Poster 3911 presented at the 2009 Oncology Nursing Society Congress in San Antonio, TX. The Efffect of an Oral Care Protocol on the Incidence and Severity of Chemo-Induced Oral Mucositis. Oncol Nurs Forum. 2009;36: 53-54. http://ons.metapress.com/content/b768w05v4u151322/fulltext.pdf
Interviewed by Carolyn Grande, MSN, CRNP, AOCNP®, an oncology nurse practitioner at the Abramson Cancer Center at the Hospital of the University of Pennsylvania and a member of the www.manageCRC.com Advisory Panel.