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Oral Complications of Cancer Therapy

Oral Complications of Cancer Therapy

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, allopurinol, glutamine, pentoxifylline, vitamin E,
beta-carotene, azelastine (Astelin), amifostine (Ethyol), misoprostol (Cytotec),
benzydamine (Tantum), immunoglobulin, chlorhexidine, povidone iodine,
nonabsorbable antibiotic lozenges, keratinocyte growth factor, interleukin
(IL)-11, granulocyte colony-stimulating factor (G-CSF [Neupogen]), and oral

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.[1]

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.[2] These authors reported
virtually identical findings, with approximately a 50% reduction in mucositis in
the group receiving the oral cryotherapy.


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