Topical chemoprevention of oral cancer with tretinoin "biofilm".

BACKGROUND

Oral cancer is a common malignancy. Chemoprevention is a promising treatment strategy but it produces systemic toxic effects. Topical application of chemopreventive agents is an attractive alternative that reduces toxic effects. This study is based on the hypothesis that topical application of mucosal adhesive film (MAF), as a means to deliver tretinoin, is effective and safe for oral cancer chemoprevention.

SETTING

Randomized animal study conducted at the Boston University School of Medicine.

DESIGN

This study uses the hamster cheek-pouch model to test efficacy and safety of the MAF/tretinoin patch for oral cancer prevention. The oral mucosa of 36 hamsters was painted with dimethylbenzanthracene to produce premalignant lesions. The 36 hamsters were divided into 3 groups of 12 hamsters each as follows: (1) control, no treatment; (2) systemic tretinoin (5.0 mg/kg per day, intraperitoneally); and (3) topically applied MAF/tretinoin patch (0.45 mg tretinoin/cm2, once daily). Treatments continued for 40 days.

MAIN OUTCOME MEASURES

Tumor growth and burden were measured over time. The duration of MAF patch retention on mucosa and local tissue reaction to the treatment were also evaluated.

RESULTS

The patch stayed on the mucosa for at least 5 hours with no evidence of inflammatory or other adverse reactions from the treated tissue. There was a significant difference in the tumor growth measurement between the control and systemic tretinoin groups (P<.001), and between the control and MAF patch groups (P<.001).

CONCLUSIONS

This is the first study, to our knowledge, to use a polymer MAF technique for oral cancer prevention. The MAF/tretinoin patch is safe and effective for such chemoprevention in the hamster model.