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.

PURPOSE: This study evaluated the safety and efficacy of recombinant human intestinal trefoil factor (rhITF) administered as topical oral spray for prevention and treatment of chemotherapy-induced oral mucositis (OM). PATIENTS AND METHODS: Ninety-nine patients with colorectal cancer who had moderate to severe OM (WHO grade >or= 2) in the first cycle of chemotherapy were randomly assigned to receive either placebo, rhITF 10 mg/mL (ie, low dose), or rhITF 80 mg/mL (ie, high dose) by oral spray (300 microL, eight times each day) for 14 consecutive days in the second chemotherapy cycle. Patients were assessed on days 1, 3, 5, 7, 10, 12, 14, and 21 (+/- 2 days for the last assessment) for safety and for OM incidence and severity. RESULTS: Treatment of patients at high risk for developing OM with low- or high-dose rhITF significantly reduced the amount of incidence (75% to 81%; low-dose rhITF P < .001; high-dose rhITF P = .002). Frequencies of WHO grade >or= 2 OM in the placebo, low-dose rhITF, and high-dose rhITF groups were 48.5%, 9.1%, and 12.1%, respectively. Assessment of the area under the curve revealed statistically significant reductions in OM severity in the rhITF-treated groups versus placebo. Only a minority of patients (6.1%) reported treatment-emergent adverse events (TEAEs), all of which were mild to moderate in intensity and resolved without sequelae. The incidence of TEAEs was not significantly different among treatment groups. CONCLUSION: rhITF oral spray formulation was safe and effective when used for the reduction of chemotherapy-associated OM in patients with colorectal cancer. Patients exhibited high compliance in dosing administration. Future clinical study is planned to develop this drug for use in OM management in patients with cancer.

Intestinal trefoil factor/TFF3 promotes re-epithelialization of corneal wounds.

Disorders of wound healing characterized by impaired or delayed re-epithelialization are a serious medical problem. These conditions affect many tissues, are painful, and are difficult to treat. In this study using cornea as a model, we demonstrate the importance of trefoil factor 3 (TFF3, also known as intestinal trefoil factor) in re-epithelialization of wounds. In two different models of corneal wound healing, alkali- and laser-induced corneal wounding, we analyzed the wound healing process in in vivo as well as in combined in vivo/in vitro model in wild type (Tff3(+)(/)(+)) and Tff3-deficient (Tff3(-)(/)(-)) mice. Furthermore, we topically applied different concentrations of recombinant human TFF3 (rTFF3) peptide on the wounded cornea to determine the efficacy of rTFF3 on corneal wound healing. We found that Tff3 peptide is not expressed in intact corneal epithelium, but its expression is extensively up-regulated after epithelial injury. Re-epithelialization of corneal wounds in Tff3(-/-) mice is significantly prolonged in comparison to Tff3(+/+) mice. In addition, exogenous application of rTFF3 to the alkali-induced corneal wounds accelerates significantly in in vivo and in combined in vivo/in vitro model wound healing in Tff3(+/+) and Tff3(-/-) mice. These findings reveal a pivotal role for Tff3 in corneal wound healing mechanism and have broad implications for developing novel therapeutic strategies for treating nonhealing wounds.