13-cis-Retinoic Acid in the Treatment of Oral Leukoplakia

Abstract

13-cis-Retinoic acid has been reported to be effective in treating oral leukoplakia. We randomly assigned 44 patients with this disease to receive 13-cis-retinoic acid (24 patients) or placebo (20), 1 to 2 mg per kilogram of body weight per day for three months, and followed them for six months. There were major decreases in the size of the lesions in 67 percent (16 patients) of those given the drug and in 10 percent (2 patients) of those given placebo (P = 0.0002); dysplasia was reversed in 54 percent (13 patients) of the drug group and in 10 percent (2 patients) of the placebo group (P = 0.01). The clinical response to the drug correlated with the histologic response in 56 percent (9 of 16) of the patients evaluated. Relapse occurred in 9 of 16 patients two to three months after treatment ended. The toxic effects of the drug were acceptable in all but two patients. Cheilitis, facial erythema, and dryness and peeling of the skin were common; conjunctivitis and hypertriglyceridemia also occurred. All adverse reactions could be reversed by reducing the dose or temporarily discontinuing the drug. We conclude that 13-cis-retinoic acid, even in short-term use, appears to be an effective treatment for oral leukoplakia and has an acceptable level of toxicity.

Formulation and In-Vitro and In-Vivo Evaluation of a Mucoadhesive Gel Containing Freeze Dried Black Raspberries: Implications for Oral Cancer Chemoprevention

“…Many of these studies resulted in some degree of clinical success (6,7,(20)(21)(22)(23)(24). Critical evaluation of the clinical trials data, however, provides a strong rationale to evaluate other chemopreventive compounds.…”

“…Critical evaluation of the clinical trials data, however, provides a strong rationale to evaluate other chemopreventive compounds. Retinoid use was associated with significant toxicities that included mucositis, conjunctivitis, dry skin and hypertriglyceridemia (20)(21)(22)(23)(24). Also apparent from the synthetic retinoid trials was the transient nature of any clinical response (23,24).…”

American Society of Preventive Oncology Distinguished Career Achievement Lecture 2006—Enjoy the Journey: The Long and Winding Road of Chemoprevention Agent Development

“…This led me to the exploration of retinoids as therapeutic modalities in a number of malignant conditions with the identification of activity in several epithelial malignancies (2)(3)(4)(5), particularly squamous cell carcinoma and preneoplastic lesions of the skin (3,4), as well as in cutaneous T-cell lymphoma (6). These positive results provided strong clinical support for our own subsequent work in chemoprevention of cervical intraepithelial neoplasia and for those investigators who later undertook chemoprevention trials of retinoids in oral leukoplakia and secondary head and neck cancers (7,8) as well as for the prevention of squamous cell cutaneous cancers and actinic keratoses (9)(10)(11).…”

Assessing Efficacy in Early-Phase Cancer Prevention Trials: The Case of Oral Premalignancy

“…The accessibility to repeated measurements and biopsy, as well as a strong association with oral cancer, identifies oral premalignant lesions such as leukoplakia and erythroplakia as excellent model systems for the study of chemopreventive interventions. Oral premalignant lesions progress to squamous cell carcinoma at a rate of 17% to 36% within 8 years (15); they regress at a rate of from 10% to 30% (16,17). In patients with oral leukoplakia, ∼60% of cancers develop in the site of the original lesion, providing a rationale both for local targeting of the lesions (to extirpate the cause of 60% of cancers) and for systemic treatment (to prevent the 40% of cancers arising beyond the original lesion site; ref.…”