Bañez Lionel L, Blake Gary W, McLeod David G, Crawford E David, Moul Judd W
Division of Urologic Surgery and the Duke Prostate Center, Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA.
BJU Int. 2009 Aug;104(3):310-4. doi: 10.1111/j.1464-410X.2009.08400.x. Epub 2009 Feb 23.
To compare the efficacy and tolerability of peripheral androgen blockade using combined low-dose flutamide plus finasteride vs low-dose flutamide monotherapy for treating biochemical relapse after the definitive management of prostate adenocarcinoma.
Fifty-six men treated for biochemical relapse of prostate cancer were enrolled prospectively in a phase II trial at the Walter Reed Army Medical Center from 1997 to 2001. Thirty-six men were treated with flutamide (125 mg twice daily) and finasteride (5 mg twice daily), and 20 men received low-dose flutamide only after biochemical recurrence (prostate-specific antigen, PSA, level > or =0.4 ng/mL). Cox proportional hazards analyses were used to compare the risk of progression between the groups.
Patients on combined and monotherapy had a median follow-up of 54 and 43.5 months, respectively. Seven men (19%) in the combined arm remain in the study with no progression, while five (25%) on monotherapy continue and are progression-free. Men on combined therapy had a greater decrease in their PSA level (P = 0.002). Multivariate analysis showed that men on combined therapy had significantly less risk of progression than men on monotherapy (hazard ratio 0.21, 95% confidence interval 0.07-0.63, P = 0.005). There was no significant difference in the frequency of side-effects between the groups. Toxicities were reported to be mild.
Our analysis suggests the therapeutic value of low-dose flutamide alone or combined with finasteride as first-line agents in a possible graduated approach for treating PSA-only recurrent prostate cancer. Due to unwanted metabolic effects associated with traditional hormonal agents, phase III trials comparing both regimens with current therapies are warranted.
比较低剂量氟他胺联合非那雄胺与低剂量氟他胺单药治疗前列腺腺癌根治术后生化复发的疗效和耐受性。
1997年至2001年，56例因前列腺癌生化复发接受治疗的男性前瞻性纳入沃尔特里德陆军医疗中心的一项II期试验。36例男性接受氟他胺（每日两次，每次125mg）和非那雄胺（每日两次，每次5mg）治疗，20例男性在生化复发（前列腺特异性抗原，PSA，水平≥0.4ng/mL）后仅接受低剂量氟他胺治疗。采用Cox比例风险分析比较两组之间的进展风险。
联合治疗组和单药治疗组患者的中位随访时间分别为54个月和43.5个月。联合治疗组中有7例男性（19%）仍在研究中，无疾病进展，而单药治疗组中有5例（25%）仍在继续治疗且无疾病进展。联合治疗组男性的PSA水平下降幅度更大（P = 0.002）。多变量分析显示，联合治疗组男性的进展风险显著低于单药治疗组男性（风险比0.21，95%置信区间0.07 - 0.63，P = 0.005）。两组之间副作用的发生频率无显著差异。据报道，毒性反应较轻。
我们的分析表明，低剂量氟他胺单独或与非那雄胺联合作为一线药物，在可能的分级治疗方法中，对于仅PSA复发的前列腺癌具有治疗价值。由于传统激素药物存在不良代谢影响，有必要进行III期试验，将这两种方案与现有疗法进行比较。
