Topical application of a mucoadhesive freeze-dried black raspberry gel induces clinical and histologic regression and reduces loss of heterozygosity events in premalignant oral intraepithelial lesions: results from a multicentered, placebo-controlled clinical trial.
OBJECTIVE
Approximately 30% higher grade premalignant oral intraepithelial neoplasia (OIN) lesions will progress to oral cancer. Although surgery is the OIN treatment mainstay, many OIN lesions recur, which is highly problematic for both surgeons and patients. This clinical trial assessed the chemopreventive efficacy of a natural product-based bioadhesive gel on OIN lesions.


METHODS
This placebo-controlled multicenter study investigated the effects of topical application of bioadhesive gels that contained either 10% w/w freeze-dried black raspberries (BRB) or an identical formulation devoid of BRB placebo to biopsy-confirmed OIN lesions (0.5 g × q.i.d., 12 weeks). Baseline evaluative parameters (size, histologic grade, LOH events) were comparable in the randomly assigned BRB (n = 22) and placebo (n = 18) gel cohorts. Evaluative parameters were: histologic grade, clinical size, and LOH.


RESULTS
Topical application of the BRB gel to OIN lesions resulted in statistically significant reductions in lesional sizes, histologic grades, and LOH events. In contrast, placebo gel lesions demonstrated a significant increase in lesional size and no significant effects on histologic grade or LOH events. Collectively, these data strongly support BRB's chemopreventive impact. A cohort of very BRB-responsive patients, as demonstrated by high therapeutic efficacy, was identified. Corresponding protein profiling studies, which demonstrated higher pretreatment levels of BRB metabolic and keratinocyte differentiation enzymes in BRB-responsive lesions, reinforce the importance of local metabolism and differentiation competency.


CONCLUSIONS
Results from this trial substantiate the LOH reductions identified in the pilot BRB gel study and extend therapeutic effects to significant improvements in histologic grade and lesional size.
Authors' Affiliations: Divisions of Oral Maxillofacial Pathology & Radiology and Oral Maxillofacial Surgery & Anesthesiology, College of Dentistry, The Ohio State University; The Ohio State University Comprehensive Cancer, Columbus, Ohio; Departments of Oral & Maxillofacial Pathology and Oral & Maxillofacial Surgery, School of Dentistry, University of Louisville, Kentucky; Departments of Diagnostic Sciences and Oral and Maxillofacial Surgery, University of North Carolina at Chapel Hill School of Dentistry, Chapel Hill, North Carolina; and Division of Hematology and Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin.
Susan R
SR
Mallery
Meng
M
Tong
Brian S
BS
Shumway
Alice E
AE
Curran
Peter E
PE
Larsen
Gregory M
GM
Ness
Kelly S
KS
Kennedy
George H
GH
Blakey
George M
GM
Kushner
Aaron M
AM
Vickers
Brian
B
Han
Ping
P
Pei
Gary D
GD
Stoner
D000287:Administration, Topical; D000328:Adult; D000368:Aged; D005260:Female; D005638:Fruit / Q000737:chemistry*; D005782:Gels / Q000008:administration & dosage / Q000737:chemistry; D006801:Humans; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008517:Phytotherapy
D005782:Gels