Progressive 13-cis-retinoic acid dosage in the treatment of oral leukoplakia

16 patients with oral leukoplakia were treated with oral 13-cis-retinoic acid. The initial dose, given for 3 months, was 0.2 mg/kg/day, increasing by a further 0.2 mg/kg/day in successive 3 month cycles. The maximum dosage reached at 1.0 mg/kg/day, was given to only 2 patients (who received a total of 15 months treatment). However, 10 patients completed the cycle at 0.8 mg/kg/day (12 months treatment in total), but treatment could not continue due to toxicity (grade I and II), which was cutaneous, mucosal, and haematological (hypertriglyceridemia and hypercholesterolemia). There was grade III toxicity in the skin and mucosa in only 1 case, a patient treated at a dose of 1.0 mg/kg/day. The toxicity was reversible in all cases. 14 of the patients completed the trial. In 4 there were improvements graded as partial responses (PR) obtained at 0.2 mg/kg/day (3PR) and 0.6 (1PR) and there was one complete response (CR) obtained at 0.4 mg/kg/day. Overall there was thus an objective response rate of 36% who showed 50% or more reduction in lesion size. After the retinoic acid treatment was stopped, patients were followed-up for 12 months; 2 patients showed regression of the responses obtained after 6 and 9 months. This study shows that oral treatment with 13-cis-retinoic acid at low dosages is efficacious and with minimal toxicity. It also shows that it is not feasible to treat these patients at doses above 0.8 mg/kg/day for long periods-mainly due to poor compliance.