The painful mouth sores and ulcers that often trouble patients being treated with chemotherapy can be prevented either with ice chips or with an antiseptic mouthwash containing Chlorhexidine ( Broxo Din ), researchers said. The antiseptic has the benefit of not being restricted to use with chemotherapy agents with a short half-life, they report.

Jens Benn Sørensen at the National University Hospital in Copenhagen, Denmark and his colleagues carried out the first double-blind, placebo-controlled study comparing Chlorhexidine, oral cooling with ice-chips ( cryotherapy ) and placebo.

Painful sores and ulcers in the lining of the mouth, known as oral mucositis, are major problems for chemotherapy patients, Sørensen says. Overall, about 40% of patients given bolus chemotherapy containing the common drug 5-FluoroUracil ( 5-FU ) may suffer the conditions.

" Patients suffering from this complication have difficulty eating and swallowing. In the most severe form, they cannot eat or drink at all and must receive nutrition and fluid replacement through tubes into the stomach or intravenously," Sørensen explains. " It is clear that this toxicity is considered very troublesome by the patients."

Physicians have sometimes used a mouth rinse with the antiseptic Chlorhexidine as a prevention against oral mucositis, but its value has been uncertain: it has been beneficial in some studies, but possibly detrimental in others.

" This uncertainty may partly be due to the various clinical scenarios in which it has been tested, " Sørensen explains. Chlorhexidine has been tried as a preventative and treatment for oral mucositis caused by radiation or chemotherapy, various cytostatic agents, conventional and high-dose chemotherapy regimens, and various patient populations such as adults with solid tumors, hematological malignancies, pediatric patients and so on. Another source of confusion is the variability of the dose and frequency of mouth rinse regimens.

To clarify the situation, the Danish team studied the value of Chlorhexidine and oral cooling only in the preventive setting, in patients with gastrointestinal cancer who were being treated with bolus 5-FluoroUracil 425 mg/m2 with Leucovorine 20 mg/m2 daily over five days.

Each patient was randomly assigned, after giving informed consent, to either Chlorhexidine 0.1% 15 ml mouth rinse for one minute three times daily for three weeks, or normal saline with same taste additive as in the Chlorhexidine group, or to cryotherapy with crushed ice, 10 minutes before to 35 minutes after chemotherapy.

Oral cooling with ice chips ( cryotherapy ) is a technique in which patients swish crushed ice around in their mouths for 45 minutes during chemotherapy. This diminishes the amount of chemotherapy which reaches the oral mucosa if the chemotherapy is cleared from the blood before the cryotherapy stops.

Among 225 patients who took part, 206 answered a questionnaire on the severity and duration of mucositis. Mucositis that was bad enough to impair eating or require artificial nutrition occurred in 13% of the Chlorhexidine group, 33% of those given placebo and 11% of those who used ice chips. Median duration of the sores and ulcers were 3 days in Chlorhexidine group, 5 days for those taking placebo and 1 day among those taking ice chips.

Both the Chlorhexidine and cryotherapy treatments reduced frequency and duration of oral mucositis when used as a preventative, the researchers found. While ice chips are easy and inexpensive to use, they are drug- and schedule-dependent and cannot be used with infusional 5-FU or with chemotherapy with substantially longer half-lives than 5-FU.

" The current study is the first double-blind randomized evaluation of Chlorhexidine in a large patient population treated homogeneously with one single chemotherapy regimen of highly mucositis inducing potential," Sørensen says. " The results point towards a role for Chlorhexidine in prevention of oral mucositis in adult patients with solid tumors treated with chemotherapy in conventional doses, without having the disadvantage of being restricted to use with chemotherapy agents with a short half-life such as is the case for cryotherapy."

Source: 31st Congress of European Society for Medical Oncology ( ESMO ), 2006

XagenaMedicine2006