Studer U E, Jenzer S, Biedermann C, Chollet D, Kraft R, von Toggenburg H, Vonbank F
Department of Urology, University of Berne, Geneva.
Eur Urol. 1995;28(4):284-90. doi: 10.1159/000475068.
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.
维生素A及其衍生物类视黄醇具有抗增殖作用，并可能诱导细胞分化。依曲替酯是一种合成视黄醇，在实验中其治疗指数比全反式维甲酸或13 - 顺式维甲酸更有利。90例Ta期和T1期浅表乳头状膀胱肿瘤患者在瑞士进入了一项前瞻性随机双盲多中心试验。其中79例患者符合条件，每天口服25毫克依曲替酯或安慰剂。在研究的第一年，安慰剂组因治疗失败而提前退出的患者数量明显更多，导致该组出现二次阳性选择。高危患者被排除，低危患者留存。在随机分组后出现肿瘤复发的患者中，两组首次复发的时间相似，安慰剂组和依曲替酯组分别为13.5个月和13.6个月。然而，依曲替酯组后续肿瘤复发的平均间隔时间明显更长。这些亚组中复发之间的平均间隔在安慰剂组为12.7个月，在依曲替酯组为20.3个月（p = 0.006）。因此，依曲替酯组每位患者每年的经尿道切除术数量也显著减少（p < 0.001）。在随机分组前接受过不止一次乳头状肿瘤经尿道切除术的患者中，安慰剂组30例患者的年度经尿道切除率从1.7降至1.3（无统计学意义，p = 0.1），依曲替酯组25例患者的年度经尿道切除率从2.1降至0.95（p < 0.001）。依曲替酯的副作用（唇炎、粘膜和皮肤干燥）对大多数患者来说是可以接受的。在依曲替酯组观察到的3例心肌梗死与视黄醇的关系尚不清楚。尽管类视黄醇对浅表乳头状膀胱肿瘤的复发率有显著影响，但在更多了解其剂量 - 毒性特征之前，类视黄醇仅应在严格控制的前瞻性试验中使用。
