剂量升级研究静脉estramustine磷酸盐结合紫杉醇和卡铂在晚期前列腺癌患者。

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凯利周、朱AX,谢尔H,科里T,法伦M, Slovin年代,施瓦茨L,拉尔森年代,通W, Hartley-Asp B, C Pellizzoni, Rocchetti M

剂量升级研究静脉estramustine磷酸盐结合紫杉醇和卡铂在晚期前列腺癌患者。

癌症研究杂志2003年6月,9 (6):2098 - 107。

PubMed ID

12796374 (在PubMed

]

文摘

目的:目的是确定一个安全周剂量的静脉输液estramustine磷酸(EMP)结合每月每周紫杉醇和卡铂在晚期前列腺癌患者。实验设计:晚期前列腺癌患者(阉割和noncastrate)管理升级的每周1小时输液注射剂量。电磁脉冲(500-1000-1500毫克/米(2))结合每周紫杉醇(100毫克/米(2)/ (1 h)和静脉输液卡铂(曲线下的面积6毫克/ ml-min每4周)。四个星期的治疗被认为是一个周期。在前三个军团,EMP增长值紫杉醇前3 h。军团4和5逆转政府秩序:电磁脉冲(剂量1000 - 1500毫克/米(2))被注入结束后立即紫杉醇。等离子体水平的EMP及其代谢物,estramustine estromustine,监控时间0,在120分钟,大约20岁,21岁,从一开始就和168 h的EMP输液。紫杉醇浓度测定在基底(0),30岁,60岁,90年和120年分和18 h紫杉醇输液开始后,和曲线估计。药代动力学评价进行周期1和2在治疗的第一个星期。结果:19例进入初始三个剂量水平(组1 - 3)。Dose-limiting瞬态肝毒性中遇到群3 (EMP = 1500毫克/米(2))。 An additional 13 patients were treated with paclitaxel (100 mg/m(2)) first, followed by i.v. EMP at 1000 mg/m(2) (cohort 4), and 1500 mg/m(2) (cohort 5). No dose-limiting toxicities were seen, and cohort 5 was determined safe for Phase II studies. Thromboembolic events were observed in 9% of patients (no prophylactic coumadin was used). Plasma concentrations of EMP and metabolites increased proportionally with dose. In all cohorts, there was a slight decrease in EMP and estramustine plasma concentrations between cycles 1 and 2. Although not significant, higher levels of estromustine at cycle 2 were observed in comparison to cycle 1. Decreased clearance of paclitaxel leading to higher than expected paclitaxel plasma concentrations was observed during the first cycle of therapy. Paclitaxel plasma concentrations were lower during cycle 2. In 17 patients with androgen-independent disease, 59% had >/=50% posttherapy decline in PSA and 22% showed measurable disease regression. CONCLUSIONS: The regimen of weekly i.v. EMP in combination with paclitaxel and carboplatin can be safely administered with hepatic toxicity being transient and reversible. Pharmacokinetic results suggest that EMP competitively inhibits the biotransformation of paclitaxel after the first administration. This effect is counterbalanced, after repeated administrations, by a possible induction of the metabolic system caused by EMP. Phase II testing is ongoing to evaluate the efficacy of this combination.

DrugBank数据引用了这篇文章

药物酶

药物	酶	类	生物	药理作用	行动
Estramustine	细胞色素P450 3 a4	蛋白质	人类	未知的	底物	细节