Mucositis or inflammation of the mucous membranes is one of the most common complications of cancer treatment. This condition is often underestimated and involves the entire gastrointestinal tract. Oral mucositis can result in significant morbidity and for this reason properly managing oral mucositis can have a significant impact on the patient’s quality of life. With the breakdown in the mucosal barrier, patients with severe myelosuppression and mucositis can potentially contract serious infections, requiring hospitalization1. Further, appropriate management of oral mucositis will allow optimal treatment of the patient’s cancer without treatment interruptions.

Pathogenesis of Mucositis

It involves the production of reactive oxygen species (ROS) which damages the mucosal cells and its vasculature, followed by active inflammation, ulceration, and subsequent healing2,3. Genetics may also play a role in increasing the incidence and duration of mucositis in certain individuals4,5.

WHO (World Health Organization) Mucositis Scale

Grade 1 – Oral Soreness,Erythema

Grade 2 – Ulcers but able to eat solids

Grade 3 – Oral ulcers and able to take liquids only

Grade 4 – Oral alimentation impossible

The risk to develop mucositis can be Treatment Related or Patient Related

Risk Factors-Treatment Related

1. Multiple cycles of chemotherapy with agents such as 5-FU, Methotrexate, Cisplatin and Cyclophosphamide.

2. Concurrent chemotherapy and radiation

3. Myeloablative therapy and Transplantation

Risk Factors-Patient Related

1. Women are at a greater risk6

2. African Americans tend to have a lower incidence of mucositis with Fluorouracil than Caucasians7

3. Oral mucosa dryness

4. Irritation and trauma caused by ill fitting dentures

5. Dental hygiene

Prevention of Oral Mucositis

• Oral hygiene should be rigorously maintained by flossing every day, brushing teeth with a soft toothbrush twice a day and rinsing the mouth with bland rinses such as normal saline, baking soda or water.

• Cryotherapy (Ice chips) for 30 minutes before and for 4 to 6 hours after therapy. Cryotherapy causes vasoconstriction resulting in decreased drug delivery to the oral mucosa8.

• KEPIVANCE® (Palifermin), a keratinocyte growth factor, given IV, only for patient’s undergoing myeloablative therapy and transplantation9. This agent increases the thickness of the mucosa.

• ETHYOL® (Amifostine), an organic, thiophosphate given IV, which scavenges reactive oxygen species (ROS), thereby reducing toxicity to the normal mucosa. It is recommended for prevention of xerostomia associated with head and neck radiation, as well as mucositis associated with high-dose melphalan. It is also approved for the prevention of renal toxicity associated with platinum compounds10.

Treatment of Oral Mucositis

• Bland rinses as mentioned above

• Topical anesthetics such as lidocaine viscous or gel

• Magic mouthwash, which is a combination of viscous lidocaine, nystatin, diphenhydramine, and dyclonine magnesium hydroxide. When using topical anesthetics, patients should be instructed not to swallow or gargle, as this can impair the gag reflex and put the patient at a risk for aspiration pneumonia. No more than 25 ml of topical anesthetic is recommended over a 24 hr period, as there is a chance for systemic absorption.

• Other agents that may benefit include GELCLAIR®, MUGARD®, CAPHOSOL®, and MUCOTROL®.

• Myelosuppressed patients with severe mucositis can be at an increased risk of contracting viral and fungal infections. Prophylactic antiviral and antifungal agents must be considered along with prophylactic antibiotics and hematopoietic growth factors.

• Severe mucositis can be associated with pain. If narcotics are indicated, transdermal or liquid preparations should be considered. Managing constipation while on narcotics should not be overlooked.

• Some patients receiving radiation treatment for head and neck cancer may benefit from a prophylactic percutaneous endoscopy gastrostomy (PEG) tube.

• Patient’s with excess oral secretions secondary to mucositis may benefit from antihistamines and scopolamine patches.

• Chlorhexidine and alcohol-containing mouthwashes should be avoided.

• It is important that these patients are adequately hydrated and nourished, avoiding any food products that could traumatize the mucosa.

Reference List

1. Elting LS, Cooksley C, Chambers M, Cantor SB, Manzullo E, Rubenstein EB. The burdens of cancer therapy. Clinical and economic outcomes of chemotherapy-induced mucositis. Cancer 2003; 98(7):1531-1539.

2. Sonis ST. Pathobiology of oral mucositis: novel insights and opportunities. J Support Oncol 2007; 5(9 Suppl 4):3-11.

3. Sonis ST. The pathobiology of mucositis. Nat Rev Cancer 2004; 4(4):277-284.

4. Ulrich CM, Yasui Y, Storb R et al. Pharmacogenetics of methotrexate: toxicity among marrow transplantation patients varies with the methylenetetrahydrofolate reductase C677T polymorphism. Blood 2001; 98(1):231-234.

5. Zhang X, Diasio RB. Regulation of human dihydropyrimidine dehydrogenase: implications in the pharmacogenetics of 5-FU-based chemotherapy. Pharmacogenomics 2007; 8(3):257-265.

6. Chansky K, Benedetti J, Macdonald JS. Differences in toxicity between men and women treated with 5-fluorouracil therapy for colorectal carcinoma. Cancer 2005; 103(6):1165-1171.

7. McCollum AD, Catalano PJ, Haller DG et al. Outcomes and toxicity in african-american and caucasian patients in a randomized adjuvant chemotherapy trial for colon cancer. J Natl Cancer Inst 2002; 94(15):1160-1167.

8. Tartarone A, Matera R, Romano G, Vigliotti ML, Di RN. Prevention of high-dose melphalan-induced mucositis by cryotherapy. Leuk Lymphoma 2005; 46(4):633-634.

9. Spielberger R, Stiff P, Bensinger W et al. Palifermin for oral mucositis after intensive therapy for hematologic cancers. N Engl J Med 2004; 351(25):2590-2598.

10. Kouvaris JR, Kouloulias VE, Vlahos LJ. Amifostine: the first selective-target and broad-spectrum radioprotector. Oncologist 2007; 12(6):738-747.