Mary Crowley Cancer Research Centers, Dallas, TX, USA.
Int J Gen Med. 2010 Dec 15;4:5-11. doi: 10.2147/IJGM.S12170.
In Phase I evaluation of CT-2103 (paclitaxel poliglumex), prolongation of prothrombin time (PT) and activated thromboplastin time (aPTT) was observed, without clinical consequence, with doses 1.3-1.5 times higher than the current clinical dose of 175 mg/m(2). This Phase I, open-label, nonrandomized pilot study was performed to study the effect of the standard dose regimen on blood coagulation.
Seven previously treated solid tumor patients received CT-2103 175 mg/m(2) intravenously on day 1 of 21-day cycles for a mean of 5.4 cycles (median 4, range 2-14). Plasma samples were collected for cycle 1 predose and at hours 1, 24, 48, and 72 after the end of administration for drug levels, and for PT and aPTT assays.
No coagulopathy-related adverse events were documented. Bleeding time remained normal in the six patients tested, with transient increases in PT and aPTT noted but resolving within 72 hours. Titration studies at 100 μg/mL of CT-2103 (corresponding to the standard clinical dose) prolonged PT and aPTT clotting times, produced a modest dose-dependent reduction of thrombin and factor Xa, and no significant changes in factors IXa, XIa, or XIIa. Two patients achieved stable disease for ≥10 cycles.
CT-2103 is associated with transient prolongation of PT and aPTT without clinical sequelae.
在 CT-2103（紫杉醇聚谷氨酸）的 I 期评估中，观察到凝血酶原时间（PT）和活化部分凝血活酶时间（aPTT）延长，但无临床后果，剂量为 1.3-1.5 倍高于目前的临床剂量 175mg/m(2)。这项 I 期、开放性、非随机试验研究旨在研究标准剂量方案对凝血的影响。
7 名先前接受过治疗的实体瘤患者接受 CT-2103 175mg/m(2)，每 21 天静脉滴注一次，平均 5.4 个周期（中位数 4，范围 2-14）。在第 1 周期给药前和给药结束后 1、24、48 和 72 小时采集血浆样本，用于药物水平检测，以及 PT 和 aPTT 检测。
未记录到与凝血功能障碍相关的不良事件。在接受测试的六名患者中，出血时间保持正常，PT 和 aPTT 短暂增加，但在 72 小时内恢复正常。在 100μg/mL 的 CT-2103（相当于标准临床剂量）浓度下进行的滴定研究延长了 PT 和 aPTT 凝血时间，导致凝血酶和因子 Xa 适度剂量依赖性降低，而因子 IXa、XIa 或 XIIa 无明显变化。两名患者稳定疾病≥10 个周期。
CT-2103 可导致 PT 和 aPTT 短暂延长，但无临床后遗症。
