Prevention of Oral Mucositis Due to 5-Fluorouracil Treatment with Oral Cryotherapy: DISCUSSION

5-FU is a synthetic analogous of pyrimidine. In the body it turns to fluorouridilate first and then to fluo-rodeoxyuridilate. 5-FU gains affectivity after this transformation. Its active metabolite prevents DNA synthesis by inhibiting thymidilate synthetase. Also, fluorouridilate formed in the body participates in the structure of RNA and disturbs this structure and protein synthesis. 5-FU has a stronger cytotoxic affect on proliferating cells than resting ones. After intravenous administration, 5-FU quickly delivers to all tissues. It has a plasma half-life ranging 5-20 minutes.

Although side effects due to chemotherapy, such as nausea and vomiting, play a role in the disturbed oral feeding, mucositis developed during chemotherapy is one of the main factors that prevents oral feeding. It is possible to prevent these side effects by med¬ical treatment. Mucositis leads to poor performance and decreases the quality of life due to insufficient feeding in patients. Preventing mucositis facilitates compliance and maintenance to cancer treatment. Mucositis does not allow giving higher doses of chemotherapy because it may affect the patient’s life span. Development of mucositis increases the risk of infection and disturbs the structure of oral mucosa epithelium, which is a natural barrier.
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As the local administration of ice pieces will cause vasoconstriction in the mucosal vessels and therefore slow down the circulation, we aimed to prevent mucositis by decreasing the exposure of oral mucosa to chemotherapeutic agents.

Allopurinol and GM-CSF were used in the treatment in order to prevent mucositis. In a study performed with GM-CSF, it has been shown that GM-CSF decreased duration and severity of the mucositis. However, allopurinol mouthwash was not found to be useful in preventing mucositis, and GM-CSF is a very expensive treatment regimen with its obscure long-term side effects. Patients treated with 5-FU-based chemotherapy showed no differences in mucositis between the sucralfate and placebo treatment. The results of a randomized controlled trial did not show any benefit of chamomile to ameliorate 5-FU induced mucositis. Prostaglandin E2 (PGE2) is suggested to possess cytoprotective properties. In a randomized, double-blind controlled trial in 60 bone marrow transplantation patients, however, there was no significant difference in the severity and duration of mucositis as well as duration of fever between the PGE2 and control groups.
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Results of initial studies evaluating the effects of cryotherapy in preventing mucositis due to 5-FU based chemotherapy regimens were promising. In our study, we considered every patient a single case, and cryotherapy was given to the same patient in one course but not given in the next. Although it is reported in the previous studies that mucositis is more frequent in younger patients, our findings are not consistent with this observation. We concluded that oral cooling prevents 5-FU-induced mucositis. When compared with other measures, this technique has some advantages: it is easy to perform, cheap and has no side effects. Prevention of oral mucositis increases tolera-bility of chemotherapy. This effective prophylactic treatment should be used in patients who are at increased risk for developing 5-FU induced mucositis. My CanadianOrder

The small sample size is the major limitation of this study, and the results must be confirmed by large-scale randomized, controlled trials. On the other hand, the combination of cryotherapy with local vasoconstrictor rinses may increase the effectiveness of the procedure, which can be a subject of future studies. Cryotherapy may also be considered a prophylactic technique in prevention of mucositis induced by other chemothera-peutic agents that have short half-lives, like 5-FU. Despite the benefits of oral cryotherapy, stomatitis is still a dose-limiting toxicity for 5-FU-based chemotherapy regimens, so efforts must be maintained to find other preventive measures or antidotes.
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Tags: 5-fluorouracil, cryotherapy, oral mucositis, prevention

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