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Description of the Evidence

continued...

Agents for the reversal or prevention of recurrence of oral lesions that sometimes progress to cancer have been evaluated, with equivocal results. A randomized controlled trial (RCT) [41] found a protective effect of fenretinide against development of relapsed and new leukoplakias during 1 year of fenretinide treatment. The study had insufficient power to determine the effect on oral cancer incidence due to premature closure of the study. Other agents have been investigated for treatment of oral premalignant lesions.[42,43,44,45,46,47] None have been proven to prevent progression to oral malignancy, and none can be considered part of standard care.

A systematic Cochrane group literature review summarized randomized trials of either surgical (excision, laser ablation, or cryotherapy) or nonsurgical interventions for the treatment of oral leukoplakia.[48] Despite the fact that surgery is the most common therapy for oral leukoplakia, there were no studies of this modality with untreated controls for comparison. Nine randomized trials of medical interventions met inclusion criteria, and only two were judged to have a low risk of study bias. Only two (studying topical bleomycin, oral vitamin A, or oral beta carotene) reported malignant transformation as an endpoint, and neither showed a difference between the active treatment and control study groups. All of the studies had short follow-up relative to the natural progression rate of leukoplakia; the mean follow-up was no longer than 15 months. Although intermediate endpoints, such as clinical response, were reported in seven of the trials, none of these endpoints has been validated as predictive of malignant transformation.

Several agents have been studied for the prevention of second cancers in patients previously treated for SCCHN, including oropharyngeal cancer. High-dose isotretinoin (50–100 mg/m² orally per day for 12 months) was compared to placebo in a small study of 103 such patients.[49,50] Overall survival and incidence of recurrence of the primary tumors were similar in both treatment groups. There was a statistically significant decrease in rate of second head and neck cancers in the isotretinoin group, but isotretinoin toxicity was substantial, making the use of this agent impractical at these doses. To mitigate this toxicity, low-dose isotretinoin (30 mg orally per day for 3 years) was subsequently tested in a placebo-controlled randomized trial of 1,190 patients with head and neck cancer, but there was no decrease in incidence of second primary tumors at this dose.[51] Likewise, vitamin A and N-acetylcysteine,[52] as well as alpha-tocopherol and beta carotene,[53] have shown no efficacy in RCTs for the prevention of second primary tumors of the oropharynx in patients who had been treated for either head and neck cancer or lung cancer.

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Last Updated: February 25, 2014
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