Peterson, D.E., Barker, N.P., Akhmadullina, L.I., Rodionova, I., Sherman, N.Z., Davidenko, I.S., et al. (2009). Phase II, randomized, double-blind, placebo-controlled study of recombinant human intestinal trefoil factor oral spray for prevention of oral mucositis in patients with colorectal cancer who are receiving fluorouracil-based chemotherapy. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology, 27(26), 4333–4338.

To evaluate the safety and efficacy of human intestinal trefoil factor (rh/TF) oral spray for the treatment and prevention of chemotherapy-induced oral mucositis.

Patients who had at least grade 2 oral mucositis after the first course of chemotherapy were randomized to receive placebo spray, low-dose rh/TF (10 mg/ml) spray, or high-dose rh/TF (80 mg/ml) spray. Patients had to fully recover from the mucositis prior to study entry. Patients were instructed to administer three puffs to the oral mucosa eight times daily for 14 days, beginning on the first day of the second chemotherapy cycle. Patients were to refrain from oral intake for 15 minutes after dosing.

• The sample consisted of 99 participants.
• Mean patient age was 58.7 years (SD = 9.1 years) in the placebo group, 62.1 years (SD = 8.9 years) in the low-dose group, and 56 years (SD = 7.9 years) in the high-dose group.
• The sample was composed of 58.6% females and 41.4% males.
• All patients had colon cancer and were receiving chemotherapy based on fluorouracil (5-FU). Of all participants, 85% had had prior radiotherapy; 97% had had leucovorin also.

• Multisite
• Outpatient setting
• Russia

Randomized double-blind placebo-controlled trial

World Health Organization grading system for oral mucositis

• Of all participants, 48.5% developed recurrent oral mucositis.
• Treatment with low-dose rh/TF and high-dose rf/TF, respectively, produced an 81.2% and a 75.1% reduction in WHO grade 2 or higher mucositis (p < 0.002). The proportion of patients with grade 0 mucositis was 60% in the low-dose group, 69.7% in the high-dose group, and 33.3% in the placebo group.
• Patient self-assessment reported higher frequency of mouth and throat soreness with placebo (p < 0.05) between days 6 and 11.
• Analgesic use was infrequent and not significantly different among groups.
• The safety profile of rh/TF was similar to that of placebo.

Topical administration of rh/TF was safe and effective in ameliorating symptoms of chemotherapy-induced oral mucositis.

• The sample had a small sample size, with fewer than 100 participants.
• The study was of limited duration, lasting through only one additional course of chemotherapy with 5-FU. Efficacy in the longer term and in other patient populations, with other chemotherapeutic regimens, is unknown.

The study suggests that rh/TF is a promising approach for the prevention and management of oral mucositis. Its ease of use and safety profile makes rh/TF a practical treatment. Authors did not discuss cost, which may be a consideration. Further study in other patient groups is warranted.