The retinoids studied are not effective in causing regression of CIN3 but may have some effect on CIN2. The data on CIN1 are inadequate. Retinoids are not effective in preventing progression of CIN of any grade. At the doses given for the duration of treatment studied, the retinoids were reasonably well tolerated.
The efficacy of 9-cis-retinoic acid (aliretinoin) as a chemopreventive agent for cervical dysplasia: results of a randomized double-blind clinical trial.
9-Cis-retinoic acid (aliretinoin) is a pan-retinoid receptor agonist and has been demonstrated in preclinical models to have potent chemoprevention effects. The purpose of this study was to determine the utility of using aliretinoin as a chemoprevention agent in cervical dysplasia. Patients with histological evidence of cervical intraepithelial neoplasia (CIN) 2/3 were randomized in a double-blind manner to receive high-dose aliretinoin (50 mg), low-dose of aliretinoin (25 mg), or placebo daily for 12 weeks. Compliance and side effects were monitored at various time points during therapy. At the completion of therapy, all of the patients underwent a loop procedure. Histology of pretreatment biopsies was compared with that of loop specimens. One-hundred and fourteen patients with CIN 2/3 were enrolled in the study. In the 112 patients evaluable for toxicity, headache was the most common clinical side effect and was experienced more frequently (74%) in the high-dose aliretinoin group. Eight patients withdrew from the study before completion of study medication because of unacceptable side effects. In the 104 patients evaluable for efficacy, there was no statistical difference in the rate of regression among the placebo (32%), the low-dose aliretinoin (32%), and the high-dose aliretinoin (36%) groups. (P = not significant; power 0.06). Aliretinoin at these dosages and this schedule does not appear to result in significant regression rates in CIN 2/3 patients when compared with placebo. Headache is encountered frequently and may thwart efforts to increase the dose or duration of aliretinoin in future cervical cancer chemoprevention studies. The rate of histological regression in biopsied CIN 2/3 patients is high even over a short time interval, and emphasizes the importance of having a placebo arm and an adequate sample size in cervical dysplasia chemoprevention studies.