Purpose
Approximately 30%higher-grade premalignant oral
intraepithelial neoplasia (OIN) lesions will progress to oral cancer. While
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.
Experimental Design
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 gm × 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
loss of heterozygosity (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.
Two double-blind, randomized, placebo-controlled feasibility trials of minocycline in ALS were conducted. In Trial 1, 19 subjects received 200 mg/day or placebo for 6 months; there were no significant differences in adverse events (AE). In Trial 2, 23 subjects received up to 400 mg/day in an 8-month crossover trial. The mean tolerated dose was 387 mg/day, there was a trend toward more gastrointestinal AE (p = 0.057), and blood urea nitrogen and liver enzymes became elevated (p < 0.05). Using these data, the authors have designed and launched a phase III trial.
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