Channing Laboratory, 3rd Floor, 181 Longwood Avenue, Boston, MA 02115, USA.
Clin J Am Soc Nephrol. 2010 Mar;5(3):477-83. doi: 10.2215/CJN.08111109. Epub 2010 Jan 7.
Hypertension and proteinuria are common but poorly understood renal toxicities of vascular endothelial growth factor (VEGF) receptor signaling pathway inhibitors. In this phase II study of cediranib (AZD2171) for recurrent epithelial ovarian cancer, the time course and severity of BP changes and proteinuria were characterized.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: 46 women ages 41 to 77 years were treated with cediranib. 26% had baseline hypertension. Twice-daily BP was recorded. Urinalyses were performed every 2 weeks, and in some patients proteinuria was further quantified.
31 women (67%) developed hypertension by day 3; 87% by the end of the study. 43% developed grade > or =3 hypertension. Mean systolic BP increase over 3 days was 18 mmHg. Women above the mean age (> or =57 years) had a larger rise in systolic BP by day 3 (15.9 versus 7.0 mmHg). 14 women developed proteinuria. There was a dose response (45 versus 30 mg daily). Proteinuria also developed rapidly, with 7 of 14 women developing proteinuria within 2 weeks. Only 7 of 20 women who developed grade 3 hypertension developed proteinuria.
Cediranib induced a rapid but variable rise in BP within 3 days of initiation in most patients. Proteinuria was common and also developed rapidly. The rapid development of hypertension suggests that acute inhibition of VEGF-dependent vasodilation might explain the BP rise with VEGF inhibitors. Clinicians must be vigilant in early detection and management of toxicities of this expanding drug class, especially in older patients.
血管内皮生长因子（VEGF）受体信号通路抑制剂引起的高血压和蛋白尿是常见但尚未被充分认识的肾毒性。在这项评估 Cediranib（AZD2171）治疗复发性上皮性卵巢癌的Ⅱ期临床试验中，对血压变化的时间过程和严重程度及蛋白尿进行了特征描述。
设计、地点、参与者和测量方法：46 名年龄 41 至 77 岁的女性接受了 Cediranib 治疗。26%的患者基线时存在高血压。每日记录两次血压。每 2 周进行一次尿液分析，部分患者进一步定量蛋白尿。
31 名女性（67%）在第 3 天发生高血压；87%的患者在研究结束时发生高血压。43%的患者发生了≥3 级高血压。3 天内平均收缩压升高 18mmHg。年龄高于平均年龄（≥57 岁）的女性收缩压升高幅度更大（第 3 天为 15.9mmHg 与 7.0mmHg）。14 名女性发生蛋白尿。存在剂量反应（45mg 组与 30mg 组）。蛋白尿也迅速发生，14 名女性中有 7 名在 2 周内发生蛋白尿。仅有 7 名发生 3 级高血压的女性发生蛋白尿。
Cediranib 在大多数患者开始治疗后 3 天内迅速但可变性地引起血压升高。蛋白尿常见且也迅速发生。高血压的快速发展表明，VEGF 依赖性血管舒张的急性抑制可能解释了 VEGF 抑制剂引起的血压升高。临床医生必须警惕这种不断扩展的药物类别的毒性的早期发现和管理，尤其是在老年患者中。
