title: Clinical modulation of oral leukoplakia and protease activity by Bowman-Birk inhibitor concentrate in a phase IIa chemoprevention trial.
abstract: Bowman-Birk inhibitor is a protease inhibitor derived from soybeans that has demonstrated chemopreventive activity in a number of in vitro and animal systems. We conducted a 1-month phase IIa clinical trial of Bowman-Birk inhibitor concentrate (BBIC) in patients with oral leukoplakia. BBIC was administered to 32 subjects with oral leukoplakia for 1 month. We assessed toxicity and clinical and histological response of the lesions, and oral mucosal cell protease activity (PA) and serum micronutrient levels were measured. Clinical response was determined by measurement of pre- and posttreatment individual and total lesion areas and analysis of blinded clinical judgments of photographs. On the basis of prespecified response criteria, 31% of patients achieved a clinical response (two with complete and eight with partial responses). BBIC was nontoxic in doses up to 1066 chymotrypsin inhibitory units. The mean pretreatment total lesion area decreased from 615 to 438 mm2 after BBIC treatment (P < 0.004). A linear fit of the dose-response relationship between dose of BBIC and decrease in total lesion area was suggested (P < 0.08), and analysis of blinded clinical impression from lesion photographs confirmed this relationship (P < 0.01). Overall, at all doses tested, a 24.2% decrease in total lesion area was observed following treatment (sign rank = -142; P < 0.004). High pretreatment PA was associated with greater decreases in PA after BBIC administration (P < 0.02). BBIC demonstrated clinical activity after oral administration to patients with oral leukoplakia. These results indicate that BBIC should be investigated for chemopreventive activity in a randomized clinical trial.
authors.affiliation: Department of Otolaryngology, Chao Family Comprehensive Cancer Center, University of California Irvine, Orange 92868, USA.
authors.forename: W B
authors.initials: WB
authors.lastname: Armstrong
authors.forename: A R
authors.initials: AR
authors.lastname: Kennedy
authors.forename: X S
authors.initials: XS
authors.lastname: Wan
authors.forename: T H
authors.initials: TH
authors.lastname: Taylor
authors.forename: Q A
authors.initials: QA
authors.lastname: Nguyen
authors.forename: J
authors.initials: J
authors.lastname: Jensen
authors.forename: W
authors.initials: W
authors.lastname: Thompson
authors.forename: W
authors.initials: W
authors.lastname: Lagerberg
authors.forename: F L
authors.initials: FL
authors.lastname: Meyskens
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004305:Dose-Response Relationship, Drug; D010450:Endopeptidases / Q000097:blood / Q000378:metabolism; D005260:Female; D006801:Humans; D007971:Leukoplakia / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa / Q000187:drug effects; D009062:Mouth Neoplasms / Q000188:drug therapy* / Q000517:prevention & control*; D011480:Protease Inhibitors / Q000627:therapeutic use; D016896:Treatment Outcome; D014358:Trypsin Inhibitor, Bowman-Birk Soybean / Q000627:therapeutic use*; D014361:Trypsin Inhibitors / Q000627:therapeutic use; D014801:Vitamin A / Q000097:blood; D014810:Vitamin E / Q000097:blood; D019207:beta Carotene / Q000097:blood
chemical_list: D011480:Protease Inhibitors; D014358:Trypsin Inhibitor, Bowman-Birk Soybean; D014361:Trypsin Inhibitors; D019207:beta Carotene; D014801:Vitamin A; D014810:Vitamin E; D010450:Endopeptidases