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The Management of Mucositis in 2005

European Oncology Review, 2005:27-8 DOI:

Mucositis is defined as the damage that occurs to the tissues of the alimentary canal following chemotherapy and/or radiotherapy. For many years, the literature concentrated on the damage done to the oral mucosa, namely the erythema, mouth ulcers and pain. However, other more distal parts of the alimentary canal are affected, particularly the oesophagus and small intestine, but also the colon and rectum. In each area, pain is a manifestation, and in distal damage diarrhea, abdominal bloating and rectal bleeding can also occur. High dose chemotherapy, prior to stem cell or bone marrow transplantation and head and neck radiotherapy, have the highest frequency of severe mucositis for the number of patients treated (50% to 90%). However, the enormous numbers of patients receiving multicycle standard dose chemotherapy mean that standard dose chemotherapy actually causes the bulk of the problem even though the frequencies are much lower (10% to 30%). Up until very recently, treatment of mucositis was merely palliative, with the use of analgesics, mouth washes and treatment reductions or delays. In 2004, the US Food and Drug Administration (FDA) approved the first agent (Palifermin) for the reduction of mucositis in transplant patients with haematological malignancies.However, there is still no licensing of any agents for use in solid tumours and multi-cycle chemotherapy or radiotherapy.
Measuring Mucositis
There are many scales available for assessing oral mucositis, and only a few for the assessment of the rest of the alimentary canal. The discrepancy is partly to do with the inaccessibility of the distal parts of the gastrointestinal tract and partly to do with the greater incidence of oral compared with more distal mucositis. The scales range from those that are easy to use in the clinic on a daily basis, such as the World Health Organization (WHO) and National Cancer Institute Common Toxicity Criteria (NCI/CTC) scores, and those that are suited more to intensive research where highly trained investigators are performing the assessments. The FDA has recognised the utility of the WHO score in registration trials for oral anti-mucotoxics, and the NCI/CTC are used for the rest of the gastrointestinal tract (see Table 1).
Epidemiology and Impact on Healthcare System
Measuring the exact incidence and severity of alimentary mucositis is very difficult. These particular toxicities are often only reported as a secondary endpoint in clinical trials, and this can lead to underpowering to detect the true incidence. Well designed, prospective trials, particularly of the newer anti-cancer agents, are required to determine the total burden of this problem. However, in its recent review of the literature, the Mucositis Study Group of Multinational Association of Supportive Care in Cancer (MASCC) did report the incidence of grade 3 or 4 mucositis for various common regimens. The incidences of grade 1 to 2 mucositis were not felt to be reliably reported. While the incidence of gastrointestinal (GI) mucositis was generally lower than that of oral mucositis (OM) there were exceptions, such as Irinotecan, where GI mucositis is much more common than OM. Risks of grade 3 to 4 mucositis ranged from <10% with the anthracyclines to >15% with 5-Fluorouracil (5-FU). 5-FU and Irinotecan combined had GI mucositis rates >30%. If total body irradiation was used with high dose chemotherapy, the rates of OM exceeded 60%.
While these rates for standard dose chemotherapy may seem low, the implications for healthcare costs are enormous. In the presence of Grade 3 to 4 mucositis, 35% of patients will have a dose delay, 60% will have a dose reduction and 30% will have the treatment stopped all together. More than 50% will also need feeding tubes and/or admission to hospital. The incidence of fever is approximately 60%. Opioid analgesic requirements also rise, and the costs per cycle rise by approximately US$5,500.
  1. Spielberger R et al., “A Phase 3, Randomized, Double-Blind, Placebo-Controlled Trial of Palifermin for Reduction of Mucositis in Patients With Hematologic Malignancies Undergoing TBI With High-Dose Chemotherapy With Auto- PBPCT”, N. Engl. J. Med. (2004);351: p. 2,590.
  2. Spielberger R et al., “A phase 3, randomized, double-blind, placebo-controlled trial of palifermin for reduction of mucositis in patients with hematologic malignancies undergoing TBI with high-dose chemotherapy with auto-PBPCT”, N. Engl. J. Med. (2004);351: p. 2,590.