Vitamin A and its derivatives, the
retinoids, have antiproliferative effects and may induce cellular differentiation.
Etretinate, a synthetic
retinoid, has a more favorable therapeutic index experimentally than
all-trans-retinoic acid or
13-cis-retinoic acid. Ninety patients with superficial papillary
bladder tumors stages Ta and T1 entered a prospective randomized double-blind multicenter trial in Switzerland. Seventy-nine of the patients were eligible and received either 25 mg of
etretinate or a placebo orally each day. The early withdrawal of a significantly greater number of patients in the placebo group for treatment failure during the first year of the study resulted in a secondary positive selection in this group. High-risk patients were removed and low-risk patients remained. In those patients who had
tumor recurrences after randomization, the time to first recurrence was similar in both groups with 13.5 and 13.6 months in the placebo and
etretinate groups, respectively. However, the mean interval to subsequent
tumor recurrence was significantly longer in the
etretinate group. The mean interval between recurrences in these subgroups was 12.7 months in the placebo arm and 20.3 months in the
etretinate arm (p = 0.006). Consequently, the number of transurethral resections per patient-year was also reduced significantly in the
etretinate group (p < 0.001). In patients with more than one transurethral resection of papillary
tumors before randomization, the annual transurethral resection rate in the two treatment groups dropped from 1.7 to 1.3 in the 30 patients in the placebo group (NS, p = 0.1) and from 2.1 to 0.95 in the 25 patients in the
etretinate group (p < 0.001). The side effects of
etretinate (
cheilitis, dryness of mucous membranes and skin) were acceptable to most patients. The relationship of the 3
myocardial infarcts observed in the
etretinate group to the
retinoid is not clear. Despite their significant effect on the recurrence rate of superficial papillary
bladder tumors,
retinoids should only be used in well-controlled prospective trials until more is known about their dosage-toxicity profiles.