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Effets vasculaires et rénaux des médicaments anti-angiogéniques: recommandations françaises pour la pratique

Société de néphrologie, Société française d’hypertension artérielle, Association pédagogique nationale des enseignants de thérapeutique et Fédération francophone de cancérologie digestive

  • Recommandations / Recommendations
  • Published:
Oncologie

Abstract

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.

Résumé

Les médicaments anti-angiogéniques (médicaments anti-VEGF sur le marché: bevacizumab (Avastin®), sunitinib (Sutent®), sorafénib (Nexavar®) sont de plus en plus utilisés dans le traitement de certains cancers (côlon, sein, poumon, foie et rein). Leurs effets secondaires sont mal connus des médecins. L’hypertension artérielle (HTA) est l’effet indésirable le plus fréquent. Son incidence dépend de la définition de la molécule et de la dose. Elle est généralement contrôlable par les traitements antihypertenseurs et compromet rarement la poursuite du traitement. Plus rarement, elle peut avoir des conséquences graves (HTA maligne, leucoencéphalopathie postérieure réversible, accident vasculaire cérébral, etc.). Des atteintes rénales sont moins fréquentes: protéinurie modérée le plus souvent, réversible, et plus rarement, syndrome néphrotique, insuffisance rénale aiguë, glomérulopathie proliférative, néphrite interstitielle et microangiopathie thrombotique. Allongement de l’espace QT et insuffisance cardiaque ont été observés avec des tinibs. Sur le plan thérapeutique: 1) avant l’administration d’une première dose d’un traitement anti-angiogénique, il ne faut pas retarder l’administration d’une première dose ou administrer un traitement antihypertenseur en raison d’une pression artérielle (PA) élevée; 2) le bilan initial comporte unemesure de la PA réalisée avec un appareil de mesure validé soit par le médecin traitant, soit au mieux en automesure tensionnelle (« règle des 3 », http://www.has-sante.fr), soit en mesure ambulatoire de la PA (appareil de mesure huméral validé (liste: http://afssaps.sante.fr); 3) la bandelette urinaire (et le cas échéant, quantification de la protéinurie), l’estimation de la fonction rénale (formule de MDRD simplifiée plutôt que Cockcroft et Gault) doivent être faites avant traitement et au cours du suivi; 4) la prise en charge thérapeutique se fait conformément aux recommandations (HAS HTA 2005: http://www.has-sante.fr); 5) la surveillance et la prise en charge thérapeutique se feront au mieux dans le cadre d’un travail en réseau comprenant médecin généraliste, oncologue, cardiologue et néphrologue.

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Authors and Affiliations

  1. Service de néphrologie-immunologie clinique, CHU de Tours, université François-Rabelais, 2, boulevard Tonnellé, F-37044, Tours cedex, France

    J. -M. Halimi & T. Lecomte

  2. Hôpital européen Georges-Pompidou, AP-HP, CIC Inserm, 20-40, rue Leblanc, F-75908, Paris cedex 15, France

    M. Azizi, G. Bobrie, D. Nochy & S. Oudard

  3. CHU de Reims, F-51092, Reims, France

    O. Bouché & P. Rieu

  4. Hôpital de La Pitié-Salpêtrière, AP-HP, 47-83, boulevard de l’Hôpital, F-75651, Paris cedex 13, France

    G. Deray

  5. Hôpital Avicenne, AP-HP, université Paris-XIII, 125, rue de Stalingrad, F-93009, Bobigny cedex, France

    G. des Guetz & J. -J. Mourad

  6. Hôpital Lariboisière AP-HP, Inserm, 2, rue Ambroise-Paré, F-75475, Paris cedex 10, France

    B. Levy

  7. Hôpital Henri-Mondor, AP-HP, Inserm, 51, avenue du Maréchal-de-Tassigny, F-94010, Créteil cedex, France

    D. Sahali

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  1. J. -M. Halimi
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Halimi, J.M., Azizi, M., Bobrie, G. et al. Effets vasculaires et rénaux des médicaments anti-angiogéniques: recommandations françaises pour la pratique. Oncologie 11, 476–489 (2009). https://doi.org/10.1007/s10269-009-1093-6

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