Annals of Oncology Advance Access originally published online on January 15, 2009
Annals of Oncology 2009 20(5):807-815; doi:10.1093/annonc/mdn713
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Management of hypertension in angiogenesis inhibitor-treated patients
1 Department of Nephrology, La Pitie-Salpetriere Hospital
2 Department of Cardiology, Saint Antoine Hospital
3 Department of Medical Oncology, Cochin Hospital, Paris
4 Department of Medical Oncology, Institut Gustave Roussy, Villejuif
5 Oncopharmacology Unit, Centre Antoine Lacassagne, Nice
6 Department of Medical Oncology, Pitie-Salpetriere Hospital, Paris, France
* Correspondence to: Dr H. Izzedine, Department of Nephrology, La Pitié-Salpêtrière Hospital, 47-80 Boulevard de l'Hôpital, Assistance Publique-Hopitaux de Paris, Pierre et Marie Curie University, 75013 Paris, France. Tel: +331-42177226; Fax: +331-42177232; E-mail: hassan.izzedine{at}psl.aphp.fr
Background: Hypertension (HTN) is one of the most frequent side-effects of systemic inhibition of vascular endothelial growth factor (VEGF) signaling. Its incidence and severity are dependent on the type of drugs, dose, and schedule used. The recognition of this side-effect is an important issue because poorly controlled HTN could lead to serious cardiovascular events. On another hand, HTN induced by anti-VEGF agents maybe a predictive factor of oncologic response. Knowledge of this clinical toxicity and/or therapeutic target or novel biomarker of drug activity can aid clinicians choosing the optimal and least toxic regimen suitable for an individual patient.
Methods: A Medline search was carried out using the following criteria: (i) all Medline listings as of 1 January 2000 with abstracts, (ii) English language, and (iii) Humans. The following phrases were used to query the database: (‘hypertension’, OR ‘blood pressure’) AND (‘anti-VEGF’ OR ‘VEGF inhibition’ OR ‘bevacizumab’ OR ‘sunitinib’ OR ‘sorafenib’ OR ‘VEGF Trap’). The references of each article identified were carefully reviewed for additional reference.
Results: Lifestyle modification should be encouraged. However, these nonpharmacologic strategies are not always suitable to patients with altered performance status related to metastatic cancer necessitating early drug intervention. Only one randomized study showed a beneficial effect of a calcium channel blocker use to prevent or minimize HTN secondary to antiangiogenic therapy. Nitrates looks as effective in controlling such side-effect.
Conclusions: No clear recommendation for an antihypertensive agent can be made in this context because there is a lack of controlled studies addressing the subject. Blood pressure-lowering drugs should be individualized to the patient's clinical circumstances and angiogenic inhibitors should be withheld only from patients who experienced hypertensive crisis.
Key words: angiogenesis inhibitors, anti-VEGF agents, drug, hypertension management
Received for publication August 22, 2008. Revision received October 13, 2008. Accepted for publication October 20, 2008.