Drs. Sonis and Fey provide a nice description of the problems associated with oral mucositis, information available regarding its etiology, and the cost generated by its treatment.
In their discussion of oral mucositis, the authors present a long list of theoretical antidotes, many of which offer glimpses of hope that they may be effective. None of these potential therapies, with one exception, has actually been proven to be helpful in clinical practice. The list of possible antidotes includes sucralfate(Drug information on sucralfate), allopurinol(Drug information on allopurinol), glutamine, pentoxifylline(Drug information on pentoxifylline), vitamin E, beta-carotene, azelastine(Drug information on azelastine) (Astelin), amifostine(Drug information on amifostine) (Ethyol), misoprostol(Drug information on misoprostol) (Cytotec), benzydamine(Drug information on benzydamine) (Tantum), immunoglobulin, chlorhexidine, iodine(Drug information on iodine)" target="_blank">povidone iodine(Drug information on povidone iodine), nonabsorbable antibiotic lozenges, keratinocyte growth factor, interleukin (IL)-11, granulocyte colony-stimulating factor (G-CSF [Neupogen]), and oral cryotherapy.
The only one of these approaches with proven efficacy is oral cryotherapy (noting that new data regarding keratinocyte growth factor may soon add this to the "proven efficacy" list). Drs. Sonis and Fey state that "cryotherapy with ice chips seems to be marginally beneficial in patients being treated with [fluorouracil (5-FU)]." They reference one trial that compared 30 minutes of cryotherapy with 60 minutes of cryotherapy, as opposed to referencing one of the two controlled clinical trials that established the benefit of this therapy. We would like to more definitively state that oral cryotherapy is substantially proven to be efficacious in the prevention of mucositis related to bolus-dose 5-FU chemotherapy.
The rationale behind this treatment approach is based on the fact that 5-FU has a short serum half-life (10 to 15 minutes). It was hypothesized that putting ice chips in the mouth 5 minutes before administering a 5-FU bolus injection and continuing to do so for 30 minutes would cool the oral cavity and lead to vasoconstriction. The vasoconstriction would hypothetically allow less 5-FU to get to the oral mucosa, thereby hopefully attenuating 5-FU-induced mucositis.
This hypothesis was tested in a late-1980s clinical trial, in which 95 patients were randomly assigned to either receive oral cryotherapy or not (the latter serving as a control group). All patients were receiving bolus 5-day intravenous 5-FU-based chemotherapy, and none had received prior chemotherapy. Patients randomized to oral cryotherapy placed crushed ice chips in their mouths 5 minutes prior to each dose of 5-FU. They were instructed to continuously swish the ice around in their oral cavities and replenish it before the previous mouthful had completely melted, for a total of 30 minutes. As evaluated by standard physician grading and patient questionnaires, mucositis was reduced by approximately 50% in the group receiving oral cryotherapy, compared to the control arm.
Another group independently conducted a trial to confirm or refute these findings. This group randomly allocated 84 patients, being treated with 5-FU-containing regimens, to either oral cryotherapy or a control arm. These authors reported virtually identical findings, with approximately a 50% reduction in mucositis in the group receiving the oral cryotherapy.