Vascular and renal effects of anti-angiogenic drugs: French recommendations for practice (Nephrology Society, French Arterial Hypertension Society, National Teaching Association of Therapeutics Teachers, and French-speaking Federation of Gastrointestinal Oncology)

摘要

Angiogenesis inhibitor drugs (bevacizumab, sunitinib, sorafenib, etc.) are now widely used for treatment of cancers, including colorectal, advanced renal-cell and hepatocellular carcinomas, breast cancer). Vascular and renal side-effects of the drugs are not well known. Hypertension is one of the most common side effects. Incidence of hypertension may be different among angiogenis inhibitors, and seems dose-depend. Arterial pressure can usually be controlled with antihypertensive medications, and treatment with angiogenesis inhibitors can be continued in most cases; however, serious hypertension-induced side effects were reported included malignant hypertension, stroke and reversible posterior leucoencephalopathy. Renal damage is infrequently reported: usually reversible mild or moderate proteinuria and in some rare cases nephritic syndrome, acute renal dysfunction, proliferative or collapsing glomerulonephritis, interstitial nephritis and thrombotic microangiopathy. Prolongation of the QT interval, congestive heart failure and left ventricular dysfunction have been reported in patients using tinibs. In the present guidelines, we recommend: 1) before the 1st administration of angiogenesis inhibitors: giving acute i.v. or oral antihypertensive medications in a patient with arterial pressure must be avoided; postponing the administration because of hypertension is not recommended; 2) initial workup should include ambulatory measurement of arterial pressure (by the general practitioner or by the patient using home blood pressure (3 times in the morning and in the evening during three consecutive days) with a validated (cf.: http://afssaps.sante.fr ) upper arm device. Using 24-hour ambulatory blood pressure measurement is optional; 3) urine dipstick (and quantification is positive) and estimated glomerular filtration rate (using abbreviated MDRD rather than Cockcroft-Gault formula) must be performed before treatment and regularly during follow-up; 4) therapeutic management must be done in accordance with national or international guidelines (in France: http://www.hassante.fr ); 5) Optimal care is best achieved within a network of professionals including general practitioners, oncologists, cardiologists and nephrologists.