Clinical modulation of oral leukoplakia and protease activity by Bowman-Birk inhibitor concentrate in a phase IIa chemoprevention trial

Bowman-Birk inhibitor is a protease inhibitor derived from soybeans that ha s demonstrated chemopreventive activity in a number of in vitro and animal systems, We conducted a I-month phase IIa clinical trial of Bowman-Birk inh ibitor concentrate (BBIC) in patients with oral leukoplakia, BBIC was admin istered to 32 subjects with oral leukoplakia for 1 month. We assessed toxic ity 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 i ndividual and total lesion areas and analysis of blinded clinical judgments of photographs. On the basis of prespecified response criteria, 31% of pat ients achieved a clinical response (two with complete and eight with partia l responses), BBIC was nontoxic in doses up to 1066 chymotrypsin inhibitory units, The mean pretreatment total lesion area decreased from 615 to 438 m m(2) after BBIC treatment (P < 0.004). A linear fit of the dose-response re lationship between dose of BBIC and decrease In total lesion area was sugge sted (P < 0.08), and analysis of blinded clinical impression from lesion ph otographs confirmed this relationship (P < 0.01). Overall, at all doses tes ted, a 24.2% decrease in total lesion area was observed following treatment (sign rank = -142; P < 0.004), High pretreatment PA was associated with gr eater decreases in PA after BBIC administration (P < 0.02). BBIC demonstrat ed clinical activity after oral administration to patients with oral leukop lakia, These results indicate that BBIC should be investigated for chemopre ventive activity in a randomized clinical trial.