Ornstein D K, Rao G S, Johnson B, Charlton E T, Andriole G L
Division of Urologic Surgery, Washington University School of Medicine, St. Louis, Missouri, USA.
Urology. 1996 Dec;48(6):901-5. doi: 10.1016/s0090-4295(96)00315-9.
To evaluate the efficacy of combined finasteride and flutamide therapy in men with advanced prostate cancer by determining (1) the short-term tolerability of finasteride monotherapy and its effect on serum prostate-specific antigen (PSA) and hormone (testosterone, dihydrotestosterone) levels, and (2) the effects of the addition of flutamide on tolerability and on serum PSA and hormone levels.
Thirteen hormone-naive men with advanced prostate cancer (4 with Stage D2, 1 with Stage D1, 1 with Stage D0, and 7 with rising PSA levels after radical prostatectomy [n = 2] or definitive radiation therapy [n = 5]) were initially treated with 5 mg finasteride daily. Flutamide (250 mg three times a day) was added after serum PSA levels stabilized.
Finasteride alone (median 5 weeks) had no significant effect on serum PSA levels (P > 0.05). Combined finasteride and flutamide resulted in a mean 91% reduction in serum PSA levels, with 85% of men achieving a nadir serum PSA level of less than 4.0 ng/mL and 46% achieving undetectable levels (0.2 ng/mL or less). Finasteride alone had no significant effect on serum testosterone levels (P > 0.05) but did result in a mean 74% reduction in serum dihydrotestosterone levels. Combined finasteride and flutamide resulted in a mean 56% increase in serum testosterone levels but had no additional effect on serum dihydrotestosterone levels (P > 0.05). Side effects occurred in 85% (gynecomastia or breast tenderness in 62% [8 of 13] and diarrhea in 23% [3 of 13]) of men on combined therapy. Potency was preserved in 66%. Combined finasteride and flutamide therapy was withdrawn from 15% (2 of 13) because of flutamide-induced diarrhea and from 23% (3 of 13) because of disease progression. All remaining patients (8 of 13) have serum PSA levels below 4.0 ng/mL and 4 of these 8 have undetectable levels. These men have received combined finasteride and flutamide for a median 11 months (range 6 to 19).
Finasteride monotherapy is inadequate therapy for advanced prostate cancer, but combined finasteride and flutamide may be a reasonable alternative for men with advanced prostate cancer who refuse conventional hormone therapy.
通过确定以下两点来评估非那雄胺与氟他胺联合治疗晚期前列腺癌男性患者的疗效：（1）非那雄胺单药治疗的短期耐受性及其对血清前列腺特异性抗原（PSA）和激素（睾酮、双氢睾酮）水平的影响；（2）加用氟他胺对耐受性以及血清PSA和激素水平的影响。
13例未经激素治疗的晚期前列腺癌男性患者（4例D2期，1例D1期，1例D0期，7例在根治性前列腺切除术[n = 2]或根治性放疗[n = 5]后PSA水平升高）最初每日服用5mg非那雄胺。血清PSA水平稳定后加用氟他胺（每日3次，每次250mg）。
单独使用非那雄胺（中位时间5周）对血清PSA水平无显著影响（P>0.05）。非那雄胺与氟他胺联合使用使血清PSA水平平均降低91%，85%的患者血清PSA最低点水平低于4.0ng/mL，46%的患者达到不可检测水平（0.2ng/mL或更低）。单独使用非那雄胺对血清睾酮水平无显著影响（P>0.05），但使血清双氢睾酮水平平均降低74%。非那雄胺与氟他胺联合使用使血清睾酮水平平均升高56%，但对血清双氢睾酮水平无额外影响（P>0.05）。联合治疗的患者中85%出现副作用（62%[13例中的8例]出现乳腺增生或乳房压痛，23%[13例中的3例]出现腹泻）。66%的患者性功能得以保留。因氟他胺引起的腹泻，15%（13例中的2例）患者停止使用非那雄胺与氟他胺联合治疗；因疾病进展，23%（13例中的3例）患者停止治疗。其余所有患者（13例中的8例）血清PSA水平低于4.0ng/mL，其中8例中的4例达到不可检测水平。这些患者接受非那雄胺与氟他胺联合治疗的中位时间为11个月（范围6至19个月）。
非那雄胺单药治疗晚期前列腺癌疗效不足，但非那雄胺与氟他胺联合使用对于拒绝传统激素治疗的晚期前列腺癌男性患者可能是一种合理的选择。
