ADJUVANT TREATMENT WITH A VITAMIN-A ANALOG (ETRETINATE) AFTER TRANSURETHRAL RESECTION OF SUPERFICIAL BLADDER-TUMORS - FINAL ANALYSIS OF A PROSPECTIVE, RANDOMIZED MULTICENTER TRIAL IN SWITZERLAND

Vitamin A and its derivatives, the retinoids, have antiproliferative e ffects and may induce cellular differentiation. Etretinate, a syntheti c 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 T-a and T-1 entered a pro spective randomized double-blind multicenter trial in Switzerland. Sev enty-nine of the patients were eligible and received either 25 mg of e tretinate or a placebo orally each day. The early withdrawal of a sign ificantly greater number of patients in the placebo group for treatmen t failure during the first year of the study resulted in a secondary p ositive selection in this group. High-risk patients were removed and l ow-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 recurre nce was significantly longer in the etretinate group. The mean interva l between recurrences in these subgroups was 12.7 months in the placeb o arm and 20.3 months in the etretinate arm (p = 0.006). Consequently, the number of transurethral resections per patient-year was also redu ced significantly in the etretinate group (p < 0.001). In patients wit h more than one transurethral resection of papillary tumors before ran domization, the annual transurethral resection rate in the two treatme nt groups dropped from 1.7 to 1.3 in the 30 patients in the placebo gr oup (NS, p 0.1) and from 2.1 to 0.95 in the 25 patients in the etretin ate group (p < 0.001). The side effects of etretinate (cheilitis, dryn ess of mucous membranes and skin) were acceptable to most patients. Th e 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, retino ids should only be used in well-controlled prospective trials until mo re is known about their dosage-toxicity profiles.