5-fluorouracil (5-FU) is used in the treatment of solid tumors, including stomach, colon, rectum, breast and pancreas carcinomas. One of the most common and important side effects of 5-FU is mucositis with ulcerations in the oral cavity. The addition of folinic acid to 5-FU increases the efficacy of the drug in the treatment; however, the frequency of mucositis also increases. The prevalence of mucositis in patients undergoing standard-dose chemotherapy is approximately 40%, and this ratio exceeds 50% in high-dose chemotherapy protocols. Mucositis-associated pain is one of the main sources of cancer treatment-related pain. Mucositis prevents oral feeding of the patients and deteriorates their performance. In some of the patients with mucositis, pain and oral dysfunction are of such severity that they require narcotic analgesia and supplemental nutrition. Also, worsening mucositis correlates with longer hospital stays and thereby increases the cost of cancer therapy. There are several studies concerning the prevention of mucositis in patients treated with 5-FU. It was hypothesized that cryotherapy would cause local vasoconstriction and therefore reduce the uptake of chemotherapeutic agents into mucosal cells during the short half-life of 5-FU. Mahood et al. initially tested the efficacy of cooling the oral mucosa with ice chips during bolus application of 5-FU in a randomized crossover trial and observed a 50% reduction in the severity and duration of 5-FU-induced mucositis. Subsequently, Cascinu et al. .conducted a randomized controlled trial in a sample of 84 patients receiving bolus 5-FU and demonstrated that incidence and severity of mucositis is significantly low in cryotherapy group compared with control patients.
The oral administration of allopurinol, granulocyte macrophage-colony stimulating factor (GM-CSF), sucralfate, chamomile, prostaglandins and chlorhexidine rinses were also used in the prevention of mucositis.
We investigated the effects of local cryotherapy mucositis incidence during 5-FU treatment. Several factors play a role in the development of chemotherapy induced mucositis: an interaction between epithelial and connective tissue cytokines may account for much of the mucosal injury but other factors, such as alterations in salivary immunoglobulins, proteins and electrolytes, nonspecific host defense in saliva, type and dosage of chemotherapy regiments, oral hygiene level and nutritional status of the patient, are probable causes in the development of mucositis. We aimed to investigate whether there is a preventing effect of cryotherapy on mucositis during 5-FU and folinic acid combination chemotherapy by giving oral ice chips during a course and skipping at the next course for the same patient.