Shalev M, Thompson T C, Frolov A, Lippman S M, Hong W K, Fritsche H, Kadmon D
Scott Department of Urology, Matsunaga-Conte Prostate Cancer Research Center, Houston, Texas 77030, USA.
Clin Cancer Res. 2000 Oct;6(10):3845-9.
The objective of this study was to determine whether there is any beneficial effect of oral 13-cis-retinoic acid (isotretinoin) on prostate cancer, using serum prostate-specific antigen (PSA) levels as a surrogate end point in patients with a rising serum PSA after radical prostatectomy. In the first phase, the effect of the drug on the serum PSA level was tested in 14 control patients with normal prostates. Our goal was to exclude any effect of isotretinoin on PSA secretion and metabolism and thus to validate any observed effect on PSA as indicative of anticancer activity. In the second phase, patients with rising PSA levels after radical prostatectomy and no evidence of metastatic disease were treated with oral isotretinoin at a daily dose of 1.0 mg/kg. Serum PSA levels were checked monthly for the first 4 months after initiation of treatment and every 3 months thereafter. No significant changes in serum PSA levels after 3 months of isotretinoin treatment were recorded in the control group (P = 1.000). Three of 11 postprostatectomy patients (27%) had a PSA reduction of 28%, 15%, and 6.6% after initiation of treatment that lasted for a period of 2-3 months. In two of these three patients, the PSA levels subsequently rose exponentially. Another patient displayed a stabilization of the serum PSA curve for 3 months after an initial sharp rise. No grade 3 or 4 toxicity was recorded in this group of patients. Isotretinoin had a modest, transient effect on the serum PSA level in 4 of 11 (36%) patients with a rising serum PSA after radical prostatectomy. We conclude that this drug is unlikely to be of major therapeutic benefit in prostate cancer patients when used as a single agent. However, its modest effect argues for the exploration of other, more potent retinoids for prostate cancer therapy.
本研究的目的是确定口服13-顺式维甲酸（异维甲酸）对前列腺癌是否有任何有益作用，以血清前列腺特异性抗原（PSA）水平作为前列腺癌根治术后血清PSA升高患者的替代终点。在第一阶段，在14名前列腺正常的对照患者中测试了该药物对血清PSA水平的影响。我们的目标是排除异维甲酸对PSA分泌和代谢的任何影响，从而验证观察到的对PSA的任何影响是否表明具有抗癌活性。在第二阶段，对前列腺癌根治术后PSA水平升高且无转移疾病证据的患者，以每日1.0mg/kg的剂量口服异维甲酸进行治疗。治疗开始后的前4个月每月检查血清PSA水平，此后每3个月检查一次。对照组在异维甲酸治疗3个月后血清PSA水平无显著变化（P = 1.000）。11名前列腺切除术后患者中有3名（27%）在开始治疗后PSA分别降低了28%、15%和6.6%，持续2 - 3个月。在这三名患者中的两名患者中，PSA水平随后呈指数上升。另一名患者在最初急剧上升后血清PSA曲线稳定了3个月。该组患者未记录到3级或4级毒性。异维甲酸对11名（36%）前列腺癌根治术后血清PSA升高的患者中的4名患者的血清PSA水平有适度的短暂影响。我们得出结论，当作为单一药物使用时，这种药物在前列腺癌患者中不太可能有主要的治疗益处。然而，其适度的效果表明有必要探索其他更有效的类视黄醇用于前列腺癌治疗。
