Related Experiment Video
Updated: Jun 17, 2026
Antagonistic Effect of Jiawei Shengjiang San on a Rat Model of Diabetic Nephropathy: Related to EGFR/MAPK3/1 Signaling Pathway
Published on: May 10, 2024
Rapid development of hypertension and proteinuria with cediranib, an oral vascular endothelial growth factor receptor
Emily S Robinson1, Ursula A Matulonis, Percy Ivy
1Channing Laboratory, 3rd Floor, 181 Longwood Avenue, Boston, MA 02115, USA. Erobinson11@partners.org
Background And Objectives:
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.
Results:
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.
Conclusions:
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.
Insights
Cediranib rapidly caused hypertension and proteinuria in ovarian cancer patients. Older women experienced a greater blood pressure increase, highlighting the need for vigilant monitoring of these vascular endothelial growth factor (VEGF) inhibitor toxicities.
Area of Science:
- Oncology
- Nephrology
- Pharmacology
Background:
- Hypertension and proteinuria are known renal toxicities of VEGF receptor signaling pathway inhibitors.
- These toxicities are not fully understood.
- Cediranib is a VEGF receptor signaling pathway inhibitor used for recurrent epithelial ovarian cancer.
Purpose of the Study:
- To characterize the time course and severity of blood pressure (BP) changes and proteinuria in patients receiving cediranib.
- To investigate potential correlations between age and BP changes.
- To explore dose-response relationships for cediranib-induced toxicities.
Main Methods:
- A phase II study involving 46 women (ages 41-77) treated with cediranib.
- Twice-daily BP monitoring and urinalyses every 2 weeks.
- Quantification of proteinuria in select patients.
Main Results:
- 67% of patients developed hypertension by day 3, and 87% by study end.
- 43% experienced grade > or =3 hypertension.
- Mean systolic BP increased by 18 mmHg within 3 days.
- Older patients (>=57 years) showed a larger BP rise.
- 14 women developed proteinuria, often within 2 weeks.
- A dose response was observed for proteinuria.
Conclusions:
- Cediranib induces rapid and variable hypertension and proteinuria.
- Acute inhibition of VEGF-dependent vasodilation may explain the BP rise.
- Early detection and management of these toxicities are crucial, especially in older patients.
- Vigilance is required for this expanding class of drugs.
Related Concept Videos
01:18Treatment for Pulmonary Arterial Hypertension: Endothelin Receptor Antagonists
ETs are synthesized through a complex sequence of enzymatic steps, primarily involving an enzyme referred to as endothelin-converting enzyme (ECE). Of...
01:25Antihypertensive Drugs: Direct Renin Inhibitors
01:26Treatment for Pulmonary Arterial Hypertension: Receptor Tyrosine Kinase Inhibitors and Calcium Channel Blockers
TKIs, such as imatinib (Gleevec), are particularly effective in tackling the growth and mitogenic factors that become upregulated in PAH patients. These factors contribute to the...
01:30Antihypertensive Drugs: Angiotensin II Receptor Blockers
01:30Antihypertensive Drugs: Angiotensin-Converting Enzyme Inhibitors
01:28Diabetic Nephropathy