Kirby R S, Andersen M, Gratzke P, Dahlstrand C, Høye K
St. George's Hospital, London University, London, UK.
BJU Int. 2001 Feb;87(3):192-200. doi: 10.1046/j.1464-410x.2001.02032.x.
To report an integrated analysis of two previous studies fully characterizing the clinical utility of the controlled-release gastrointestinal therapeutic system (GITS) formulation of doxazosin in the treatment of benign prostatic hyperplasia (BPH).
Two pivotal randomized, double-blind studies of doxazosin GITS for BPH were assessed by an integrated analysis. Both studies included a 2-week washout period, a 2-week single-blind placebo run-in phase, and a 13-week double-blind treatment phase. One study compared doxazosin GITS, doxazosin standard (-S) and placebo in 795 men; the other compared doxazosin GITS and doxazosin-S in 680 men. Doxazosin GITS was initiated at 4 mg once daily and titrated to 8 mg once daily after 7 weeks, and doxazosin-S was initiated at 1 mg once daily and titrated to a maximum of 8 mg once daily over 7 weeks as needed to achieve optimal symptom control. The primary outcome measures were mean changes from baseline to the final visit for the International Prostate Symptom Score (IPSS) and maximum urinary flow rate (Qmax) in the per-protocol population. Numerous symptom- and urinary-related secondary outcomes were assessed, as were effects of therapy on male erectile dysfunction measured using the International Index of Erectile Function (IIEF) in one study.
Both doxazosin GITS and doxazosin-S significantly improved the symptoms of BPH, as shown by a 45% reduction for each in total IPSS from baseline to final visit, compared with a 34% reduction in patients on placebo. Doxazosin GITS and doxazosin-S produced comparable improvements in Qmax that were significantly greater than with placebo, with a greater improvement sooner after treatment with doxazosin GITS than with doxazosin-S. Nearly half of the patients on doxazosin GITS had symptom relief at the 4-mg starting dose. A similar number of patients in both doxazosin groups were titrated to the maximum dose. Secondary outcomes were consistent with the primary effects. Both doxazosin GITS and doxazosin-S produced significant improvements in sexual function according to IIEF scores among those with dysfunction at baseline. The overall incidence of adverse events was similar among patients treated with doxazosin GITS and placebo, and slightly lower than those on doxazosin-S. There was no apparent difference in the type of adverse events reported for the two formulations of doxazosin, although most adverse events were reported at a lower frequency with doxazosin GITS.
Doxazosin GITS is significantly more effective than placebo in reducing the clinical symptoms of BPH and improving Qmax, and as effective as doxazosin-S. Both doxazosin formulations improved sexual function in patients with BPH and sexual dysfunction at baseline. Doxazosin GITS produced a therapeutic effect equivalent to that of doxazosin-S, but with fewer titration steps and a slightly lower overall incidence of adverse events.
报告一项对两项既往研究的综合分析，这两项研究全面阐述了多沙唑嗪控释胃肠道治疗系统（GITS）制剂在治疗良性前列腺增生（BPH）中的临床应用价值。
通过综合分析评估了两项关于多沙唑嗪GITS治疗BPH的关键随机、双盲研究。两项研究均包括为期2周的洗脱期、为期2周的单盲安慰剂导入期以及为期13周的双盲治疗期。一项研究在795名男性中比较了多沙唑嗪GITS、多沙唑嗪标准制剂（-S）和安慰剂；另一项研究在680名男性中比较了多沙唑嗪GITS和多沙唑嗪-S。多沙唑嗪GITS起始剂量为每日4毫克，7周后滴定至每日8毫克；多沙唑嗪-S起始剂量为每日1毫克，根据需要在7周内滴定至最大每日8毫克以实现最佳症状控制。主要结局指标是符合方案人群中从基线到最后一次访视时国际前列腺症状评分（IPSS）和最大尿流率（Qmax）的平均变化。评估了许多与症状和尿液相关的次要结局，以及在一项研究中使用国际勃起功能指数（IIEF）测量的治疗对男性勃起功能障碍的影响。
多沙唑嗪GITS和多沙唑嗪-S均显著改善了BPH的症状，从基线到最后一次访视时，两者的总IPSS均降低了45%，而安慰剂组患者降低了34%。多沙唑嗪GITS和多沙唑嗪-S在Qmax方面产生了相当的改善，显著大于安慰剂组，且多沙唑嗪GITS治疗后比多沙唑嗪-S更快出现更大改善。近一半服用多沙唑嗪GITS的患者在起始4毫克剂量时症状缓解。两个多沙唑嗪组中滴定至最大剂量的患者数量相似。次要结局与主要效应一致。根据IIEF评分，基线时有功能障碍的患者中，多沙唑嗪GITS和多沙唑嗪-S在性功能方面均产生了显著改善。服用多沙唑嗪GITS和安慰剂的患者不良事件总体发生率相似，略低于服用多沙唑嗪-S的患者。两种多沙唑嗪制剂报告的不良事件类型没有明显差异，尽管大多数不良事件在多沙唑嗪GITS组中的报告频率较低。
多沙唑嗪GITS在减轻BPH临床症状和改善Qmax方面比安慰剂显著更有效，且与多沙唑嗪-S效果相当。两种多沙唑嗪制剂均改善了基线时有BPH和性功能障碍患者的性功能。多沙唑嗪GITS产生的治疗效果与多沙唑嗪-S相当，但滴定步骤更少，不良事件总体发生率略低。
