J Clin Oncol. 2007 Jul 20;25(21):3045-54.
Phase I clinical study of AZD2171, an oral vascular endothelial growth factor signaling inhibitor, in patients with advanced solid tumors.
AZD2171作为一种口服的血管内皮生长信号因子抵制剂，其临床I期试验在带有实体瘤的晚期病人中展开。
Drevs J, Siegert P, Medinger M, Mross K, Strecker R, Zirrgiebel U, Harder J, Blum H, Robertson J, Jürgensmeier JM, Puchalski TA, Young H, Saunders O, Unger C.
人名（略）
Source
来源（略）
Tumor Biology Center, MR Development and Application Center, Albert Ludwigs University, Freiburg, Germany.drevs@sanafontis.com
Abstract
论述
PURPOSE:
目的
AZD2171 is a highly potent oral selective inhibitor of vascular endothelial growth factor (VEGF) signaling.
AZC2171是一种口服的，高有效具有选择性的血管内皮生长信号因子抑制剂。
This phase I study was designed to evaluate the safety and tolerability of increasing doses of AZD2171, with additional assessments of pharmacokinetics, pharmacodynamics, and efficacy.
该I期试验用其药物代谢动力学的评估，药物动力及有效性来衡量该药的安全性及增加剂量后使用该药的耐受性。
PATIENTS AND METHODS:
病人及开展方法
In part A, 36 patients with solid tumors and liver metastases refractory to standard therapies received once-daily oral AZD2171 (0.5 to 60 mg).
第一阶段中，36位经标准治疗后仍旧进展的带有实体肿瘤和肝转移病人接受了一天一次的口服AZD2171（剂量从0.5至60毫克）。
Doses were escalated in successive cohorts until the maximum-tolerated dose was identified.
剂量逐步增加直到确认出最大可耐受剂量。
In part B, patients with (n = 36) or without (n = 11) liver metastases were randomly assigned to receive once-daily AZD2171 (20, 30, or 45 mg).
第二阶段中，有肝转移的病人（36人）或未有肝转移的病人（11人）被随机安排接受一天一次服用AZD2171（剂量为20，30或45毫克）。
In both parts, treatment continued until tumor progression or dose-limiting toxicity (DLT) was observed.
在两个阶段中，治疗方法将持续进行直到肿瘤进展或剂量限制性毒性出现。
RESULTS:
结果
Eighty-three patients received AZD2171, which was generally well tolerated at doses of 45 mg/d or less;
83位病人在服用AZD2171后普遍表示每天服用45毫克或少于该剂量的药其耐受是良好的。the most frequently reported dose-related adverse events were diarrhea, dysphonia, and hypertension.
受反应最多的与剂量相关的不良事件有腹泻，发声困难和高血压。
The most common DLT was hypertension (n = 7), which occurred at AZD2171 doses of 20 mg and higher.
最常见的剂量限制性毒性是高血压（7人），这一现象在服用20毫克及更多的剂量时出现。
After a single dose, maximum plasma (peak) drug concentration after single-dose administration (Cmax) was achieved 1 to 8 hours postdosing with an arithmetic mean half-life associated with terminal slope of a semilogarithmic concentration-time curve (t1/2 lamda(z)) of 22 hours.
单剂量给药后，血浆中的药峰值出现在给药后的1到8小时，根据这一算法药物半衰期到代谢完成历时22小时（句中给了一个lamda公式，根据曲线得出这一结论。译者注）
Pharmacodynamic assessments demonstrated time-, dose-, and exposure-related decreases in initial area under the curve, defined over 60 seconds post-contrast arrival in the tissue (iAUC60) using dynamic contrast-enhanced magnetic resonance imaging, as well as dose- and time-dependent reductions in soluble VEGF receptor 2 levels.
药动力评估证明其与时间，剂量，照射相关，在使用动态增强核磁共振对组织部位进行60秒以上的增强影像和对可溶性VEGF 2受体进行剂量和时间减少的使用显示其在曲线下初次面积减少。
Preliminary evidence of efficacy included two confirmed partial responses and 22 patients with stable disease; effects on tumor size appeared to be dose related.
由两部分已经确认的答复及22位病人稳定的病情这一系列初步有效的证据显示，AZD2171在对于肿瘤大小的有效性上是与剂量密切相关的。
CONCLUSION:
结论
Once-daily oral AZD2171 at doses of 45 mg or less was generally well tolerated and was associated with encouraging antitumor activity in patients with a broad range of advanced solid tumors.
一天一次口服AZD2171 45毫克剂量或少于该剂量被普遍认为是可耐受且鼓励已广泛转移的晚期实体瘤病人将此作为抗肿瘤的方法。
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