Laser-assisted low-dose retinoic acid in oral cancer chemoprevention.
OBJECTIVE
Systemic retinoic acid (RA) treatment for chemoprevention of squamous cell carcinoma of the head and neck (HNSCC) is limited by RA's toxic side effects at therapeutic doses. The pulsed-dye laser (PDL), through a mechanism of selective vascular targeting, may allow reduction of the RA dose to one that is better tolerated when these treatments are used in combination. This study tests our hypothesis that combination therapy of PDL irradiation and low-dose systemic RA is as effective as high-dose RA therapy alone in the chemoprevention of HNSCC.


METHODS
Randomized, prospective study in a hamster model.


METHODS
Dysplastic lesions were induced in the cheek pouches of 48 hamsters by painting with topical 9,10-dimethl-1,2-benzanthrancene (DMBA). The hamsters were randomly divided into four treatment groups: 1) control (no treatment); 2) PDL irradiation only; 3) 5.0 mg RA (all-trans retinoid, 5.0 mg/kg per day, intraperitoneally [IP]); and (4) PDL + 0.5 mg RA (0.5 mg/kg per day, IP). The PDL irradiation was conducted at day 0 and 15, whereas the RA treatment was continued for 27 days. Tumor burden was measured over time.


RESULTS
The lesions in all of three treatment groups grow more slowly than the untreated controls. The combination treatment of PDL and RA had the greatest inhibitory effect on tumors.


CONCLUSIONS
This study suggests that combination treatment of PDL and low-dose RA is more effective than high-dose RA alone in the chemoprevention of HNSCC in a hamster cheek-pouch model, so that it should allow greatly improved tolerance of this regimen.
Driver
Mark
M
Department of Otolaryngology-Head and Neck Surgery, Boston University School of Medicine, Boston, Massachusetts, USA.
Upadhyay
Urmen D
UD
Shapshay
Stanley M
SM
Wang
Zhi
Z
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002294:Carcinoma, Squamous Cell / Q000517:prevention & control*; D002610:Cheek; D006224:Cricetinae; D004195:Disease Models, Animal; D053685:Laser Therapy; D008297:Male; D008647:Mesocricetus; D009061:Mouth Mucosa; D009062:Mouth Neoplasms / Q000601:surgery*; D011446:Prospective Studies; D011897:Random Allocation; D014212:Tretinoin / Q000008:administration & dosage*
D000970:Antineoplastic Agents; D014212:Tretinoin