醋酸曲普瑞林微球在局部晚期和转移性前列腺癌患者中的有效性、药代动力学及安全性
Effectiveness, pharmacokinetics, and safety of triptorelin acetate microspheres in patients with locally advanced and metastatic prostate cancer.
作者信息
Wu Guolan, Zhou Feng, Wang Haiping, Liu Kan, Yu Dexin, Fan Lianlian, Han Yangyun, Ai Xiaohong, Cao Youhan, Wang Xiaolin, Wang Sheng, He Chaohong, Wu Jitao, Wu Ji, Wang Youlei, Wang Yanqing, Jin Baiye, Shentu Jianzhong
机构信息
Department of Clinical Pharmacy, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, China.
出版信息
Ther Adv Med Oncol. 2024 Dec 23;16:17588359241307818. doi: 10.1177/17588359241307818. eCollection 2024.
BACKGROUND
A newly generic microspheres, sustained-release formulation of triptorelin acetate 3.75 mg has been developed.
OBJECTIVES
To evaluate the efficacy, pharmacokinetics, and safety of triptorelin 1-month formulation in Chinese patients with prostate cancer.
DESIGN
An open-label, multicenter clinical trial with one arm testing a 1-month sustained-release triptorelin formulation in prostate cancer patients.
METHODS
Patients with prostate cancer received three consecutive 28-day injections of triptorelin acetate. The primary endpoint was the proportion of successful patients over the total number of evaluable patients. Treatment success was defined as testosterone suppression below the clinical castration level (i.e., <0.5 ng/mL) at day 28 and maintenance of clinical castration until study completion (day 84). The frequency of patients with testosterone concentrations <0.2 ng/mL was also studied.
RESULTS
The study included 125 patients. All 125 patients received at least one dose of the study drug and 122 completed the study. The successful patient proportion among the evaluable patients was 97.6% (122/125; 95% CI, 92.7-99.2). 95.1% (116/122) achieved testosterone concentrations <0.2 ng/mL. The pharmacokinetic profile of triptorelin during the first 3 months of treatment, evaluated in a subset of the study population ( = 11), showed sustained release of triptorelin from the formulation. Values for AUC calculated from day 0 to 28, and day 56 to 84 were 134.42 (28.76), and 154.72 (21.86) h*ng/mL, respectively. The most common treatment-related adverse events were increased alanine aminotransferase (18.4%), increased aspartate aminotransferase (16.0%), and hot flashes (9.6%). Prolonged QT interval on electrocardiogram, erectile dysfunction, and decreased libido each occurred in ⩽4% of the patients. The frequently reported local adverse reaction was pain at the injection site, experienced by 2.4% (3/125) of the patients.
CONCLUSION
3.75-mg Triptorelin acetate microspheres for injection were effective in achieving and maintaining testosterone suppression and were well tolerated in patients with prostate cancer.
TRIAL REGISTRATION
chictr.org.cn (ChiCTR2000033188).
背景
已研发出一种新型的醋酸曲普瑞林3.75毫克长效微球制剂。
目的
评估醋酸曲普瑞林1个月制剂在中国前列腺癌患者中的疗效、药代动力学和安全性。
设计
一项开放标签、多中心临床试验，其中一个试验组对前列腺癌患者使用1个月的醋酸曲普瑞林长效制剂进行测试。
方法
前列腺癌患者连续接受三次28天的醋酸曲普瑞林注射。主要终点是成功患者占可评估患者总数的比例。治疗成功定义为在第28天时睾酮抑制至临床去势水平以下（即<0.5纳克/毫升），并维持临床去势直至研究结束（第84天）。还研究了睾酮浓度<0.2纳克/毫升的患者频率。
结果
该研究纳入125例患者。所有125例患者均接受了至少一剂研究药物，122例完成了研究。可评估患者中的成功患者比例为97.6%（122/125；95%CI，92.7 - 99.2）。95.1%（116/122）的患者睾酮浓度<0.2纳克/毫升。在一部分研究人群（n = 11）中评估的治疗前3个月期间醋酸曲普瑞林的药代动力学特征显示，该制剂中醋酸曲普瑞林呈持续释放。从第0天到第28天以及第56天到第84天计算的AUC值分别为134.42（28.76）和154.72（21.86）小时·纳克/毫升。最常见的治疗相关不良事件为丙氨酸氨基转移酶升高（18.4%）、天冬氨酸氨基转移酶升高（16.0%）和潮热（9.6%）。心电图QT间期延长、勃起功能障碍和性欲减退在≤4%的患者中出现。经常报告的局部不良反应为注射部位疼痛，2.4%（3/125）的患者出现该症状。
结论
3.75毫克注射用醋酸曲普瑞林微球在实现和维持睾酮抑制方面有效，且前列腺癌患者耐受性良好。
试验注册
chictr.org.cn（ChiCTR2000033188）
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