title: 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.
abstract: OBJECTIVE
  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).
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Oral Health and Diagnostic Sciences, School of Dental Medicine, Neag Comprehensive Cancer Center, University of Connecticut Health Center, 263 Farmington Ave, Farmington, CT 06030-1605, USA. peterson@nso.uchc.edu
authors.forename: Douglas E
authors.initials: DE
authors.lastname: Peterson
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Barker
authors.forename: Lilia I
authors.initials: LI
authors.lastname: Akhmadullina
authors.forename: Irina
authors.initials: I
authors.lastname: Rodionova
authors.forename: Nailya Z
authors.initials: NZ
authors.lastname: Sherman
authors.forename: Irina S
authors.initials: IS
authors.lastname: Davidenko
authors.forename: Galina N
authors.initials: GN
authors.lastname: Rakovskaya
authors.forename: Eugeny A
authors.initials: EA
authors.lastname: Gotovkin
authors.forename: Sergey A
authors.initials: SA
authors.lastname: Shinkarev
authors.forename: Mikhail V
authors.initials: MV
authors.lastname: Kopp
authors.forename: Eugeny P
authors.initials: EP
authors.lastname: Kulikov
authors.forename: Vladimir M
authors.initials: VM
authors.lastname: Moiseyenko
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Gertner
authors.forename: Igor
authors.initials: I
authors.lastname: Firsov
authors.forename: Tamara
authors.initials: T
authors.lastname: Tuleneva
authors.forename: Alexander
authors.initials: A
authors.lastname: Yarosh
authors.forename: Chee-Wai
authors.initials: CW
authors.lastname: Woon
mesh_terms: D015746:Abdominal Pain / Q000139:chemically induced; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D003967:Diarrhea / Q000139:chemically induced; D004311:Double-Blind Method; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006261:Headache / Q000139:chemically induced; D006801:Humans; D006973:Hypertension / Q000139:chemically induced; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000009:adverse effects / Q000235:genetics / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D013280:Stomatitis / Q000139:chemically induced / Q000517:prevention & control*; D016896:Treatment Outcome; D000071164:Trefoil Factor-2
chemical_list: D010455:Peptides; D011994:Recombinant Proteins; D000071164:Trefoil Factor-2; D005472:Fluorouracil