COMMENTARY
Lessons from Antiangiogenic Cancer Therapy–Induced Hypertension Michael Bursztyn, MD From the Department of Medicine, Hypertension Unit, Hadassah-Hebrew University Medical Center, Mount-Scopus, Jerusalem, Israel
Use of antiangiogenic therapy in patients with cancer is based on the paradigm envisioned by Folkman, emphasizing the importance of tumor-initiated neovascularization.1 This paradigm has been validated with the success of the monoclonal antivascular endothelial growth factor (VEGF) bevacizumab. Nevertheless, soon it became apparent that bevacizumab was associated with substantial cardiovascular adverse events, notably hypertension. The rapid rise of blood pressure (BP) in previously normotensive patients, ie, without time for proper vascular adaptation (eg, hypertrophy, vascular rarefaction, sodium excretion resetting) brought about exposure to high pressure of tissues unaccustomed to such pressures, manifesting at its extreme as posterior reversible leukoecephalopathy,2 as may happen in other such contexts of sudden BP rise, acute glomerulonephritis in children, and preeclampsia. More recently, orally active small multikinase inhibitors were developed and found effective in a broad variety of solid cancers, notably metastatic renal cell (RCC) and hepatocellular carcinomas, and is being tested in a wide variety of other cancers. One such drug is sorafenib, which, along with a rapidly elongating list of related drugs such as sunitinib, tovazinib, pazopanib, regorafenib, vandetanib, and axitinib, also notoriously cause BP elevation in patients treated for cancer. In this issue, Li and colleagues3 present a systematic review and meta-analysis of the incidence and risk of hypertension conferred by sorafenib, based on 13,555 patients enrolled in double-blind randomized studies (7013 patients), single-arm phase 2 studies (2881 patients), and expanded-access programs (3661 patients). They found 3 interesting findings: (1) Sorafenib therapy is associated with a 3-fold higher risk of hypertension. The incidence rate of hypertension was about 19%, but that of more serious hypertension, only 4%. (2) Patients with RCC had a higher incidence of sorafenib-induced hypertension, 24% more than those with other tumors (16%, P5 months) had higher grades of hypertension (6% vs 3% among those with a shorter than median disease-free survival, P
Lessons from Antiangiogenic Cancer Therapy–Induced Hypertension Michael Bursztyn, MD From the Department of Medicine, Hypertension Unit, Hadassah-Hebrew University Medical Center, Mount-Scopus, Jerusalem, Israel
Use of antiangiogenic therapy in patients with cancer is based on the paradigm envisioned by Folkman, emphasizing the importance of tumor-initiated neovascularization.1 This paradigm has been validated with the success of the monoclonal antivascular endothelial growth factor (VEGF) bevacizumab. Nevertheless, soon it became apparent that bevacizumab was associated with substantial cardiovascular adverse events, notably hypertension. The rapid rise of blood pressure (BP) in previously normotensive patients, ie, without time for proper vascular adaptation (eg, hypertrophy, vascular rarefaction, sodium excretion resetting) brought about exposure to high pressure of tissues unaccustomed to such pressures, manifesting at its extreme as posterior reversible leukoecephalopathy,2 as may happen in other such contexts of sudden BP rise, acute glomerulonephritis in children, and preeclampsia. More recently, orally active small multikinase inhibitors were developed and found effective in a broad variety of solid cancers, notably metastatic renal cell (RCC) and hepatocellular carcinomas, and is being tested in a wide variety of other cancers. One such drug is sorafenib, which, along with a rapidly elongating list of related drugs such as sunitinib, tovazinib, pazopanib, regorafenib, vandetanib, and axitinib, also notoriously cause BP elevation in patients treated for cancer. In this issue, Li and colleagues3 present a systematic review and meta-analysis of the incidence and risk of hypertension conferred by sorafenib, based on 13,555 patients enrolled in double-blind randomized studies (7013 patients), single-arm phase 2 studies (2881 patients), and expanded-access programs (3661 patients). They found 3 interesting findings: (1) Sorafenib therapy is associated with a 3-fold higher risk of hypertension. The incidence rate of hypertension was about 19%, but that of more serious hypertension, only 4%. (2) Patients with RCC had a higher incidence of sorafenib-induced hypertension, 24% more than those with other tumors (16%, P5 months) had higher grades of hypertension (6% vs 3% among those with a shorter than median disease-free survival, P
