Management of hypertension in angiogenesis inhibitor-treated patients.

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.

[1]  D. Nochy,et al.  VEGF inhibition and renal thrombotic microangiopathy. , 2008, The New England journal of medicine.

[2]  N. Harbeck,et al.  Randomized, double-blind, placebo-controlled, phase III study of bevacizumab with docetaxel or docetaxel with placebo as first-line therapy for patients with locally recurrent or metastatic breast cancer (mBC): AVADO. , 2008 .

[3]  D. Cunningham,et al.  Final efficacy results for bevacizumab plus standard first-line chemotherapies in patients with metastatic colorectal cancer: First BEAT , 2008 .

[4]  J. Schellens,et al.  Optimal management of emergent hypertension during treatment with a VEGF signaling inhibitor: A randomized phase II study of cediranib , 2008 .

[5]  D. Sargent,et al.  Safety and effectiveness of bevacizumab (BV) and chemotherapy (CT) in elderly patients (pts) with metastatic colorectal cancer (mCRC): Results from the BRiTE observational cohort study , 2008 .

[6]  C. Porta,et al.  Re: damien pouessel, stéphane culine. High frequency of intracerebral hemorrhage in metastatic renal carcinoma patients with brain metastases treated with tyrosine kinase inhibitors targeting the vascular endothelial growth factor receptor. Eur urol 2008;53:376-81. , 2008, European urology.

[7]  B. Lévy,et al.  Blood pressure rise following angiogenesis inhibition by bevacizumab. A crucial role for microcirculation. , 2008, Annals of oncology : official journal of the European Society for Medical Oncology.

[8]  L. Seymour,et al.  Phase I and pharmacokinetic study of daily oral AZD2171, an inhibitor of vascular endothelial growth factor tyrosine kinases, in combination with carboplatin and paclitaxel in patients with advanced non-small-cell lung cancer: the National Cancer Institute of Canada clinical trials group. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[9]  S. Culine,et al.  High frequency of intracerebral hemorrhage in metastatic renal carcinoma patients with brain metastases treated with tyrosine kinase inhibitors targeting the vascular endothelial growth factor receptor. , 2008, European urology.

[10]  A. Kudelka,et al.  Incidence and risk of hypertension with sorafenib in patients with cancer: a systematic review and meta-analysis. , 2008, The Lancet. Oncology.

[11]  S. Oudard,et al.  Home blood-pressure monitoring in patients receiving sunitinib. , 2008, The New England journal of medicine.

[12]  E. Perez,et al.  Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. , 2007, The New England journal of medicine.

[13]  Bohuslav Melichar,et al.  Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trial , 2007, The Lancet.

[14]  David Zurakowski,et al.  Cardiotoxicity associated with tyrosine kinase inhibitor sunitinib , 2007, The Lancet.

[15]  C. Porta,et al.  Uncovering Pandora’s vase: the growing problem of new toxicities from novel anticancer agents. The case of sorafenib and sunitinib , 2007, Clinical and Experimental Medicine.

[16]  J. Hainsworth,et al.  3049 POSTER Management of hypertension (HTN) in patients (pts) with metastatic colorectal cancer (mCRC) treated with bevacizumab (BV) plus chemotherapy (CT) , 2007 .

[17]  G. Martín,et al.  Reversible posterior leukoencephalopathy syndrome induced by sunitinib. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[18]  H. Izzedine,et al.  Angiogenesis inhibitor therapies: focus on kidney toxicity and hypertension. , 2007, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[19]  J. Drevs,et al.  Phase I clinical study of AZD2171, an oral vascular endothelial growth factor signaling inhibitor, in patients with advanced solid tumors. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[20]  E. Lin,et al.  Final results of CONFIRM 2: A multinational, randomized, double-blind, phase III study in 2nd line patients (pts) with metastatic colorectal cancer (mCRC) receiving FOLFOX4 and PTK787/ZK 222584 (PTK/ZK) or placebo , 2007 .

[21]  Petr Zatloukal,et al.  Randomised, double-blind multicentre phase III study of bevacizumab in combination with cisplatin and gemcitabine in chemotherapy-naive patients with advanced or recurrent non-squamous non-small cell lung cancer (NSCLC): BO17704 , 2007 .

[22]  L. Dirix,et al.  Treatment of arterial hypertension (AHT) associated with angiogenesis inhibitors. , 2007, Annals of oncology : official journal of the European Society for Medical Oncology.

[23]  H. Izzedine,et al.  Hypertension as a predictive factor of Sunitinib activity. , 2007, Annals of oncology : official journal of the European Society for Medical Oncology.

[24]  P. Catalano,et al.  Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: results from the Eastern Cooperative Oncology Group Study E3200. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[25]  Apurva A Desai,et al.  Sorafenib in advanced clear-cell renal-cell carcinoma. , 2007, The New England journal of medicine.

[26]  R. Figlin,et al.  Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. , 2007, The New England journal of medicine.

[27]  R. Pazdur,et al.  Sorafenib for the Treatment of Advanced Renal Cell Carcinoma , 2006, Clinical Cancer Research.

[28]  Robert Gray,et al.  Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. , 2006, The New England journal of medicine.

[29]  D. Webb,et al.  Effect of Regular Phosphodiesterase Type 5 Inhibition in Hypertension , 2006, Hypertension.

[30]  A. El-Khoueiry,et al.  Reversible posterior leukoencephalopathy syndrome induced by RAF kinase inhibitor BAY 43-9006. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[31]  S. Heffelfinger,et al.  Potential deployment of angiotensin I converting enzyme inhibitors and of angiotensin II type 1 and type 2 receptor blockers in cancer chemotherapy. , 2006, Anti-cancer agents in medicinal chemistry.

[32]  J. Hainsworth,et al.  Safety and efficacy of oxaliplatin/fluoropyrimidine regimens with or without bevacizumab as first-line treatment of metastatic colorectal cancer (mCRC): Final analysis of the TREE-Study. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[33]  E. Van Cutsem,et al.  Results of an interim analysis of a multinational randomized, double-blind, phase III study in patients (pts) with previously treated metastatic colorectal cancer (mCRC) receiving FOLFOX4 and PTK787/ZK 222584 (PTK/ZK) or placebo (CONFIRM 2). , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[34]  J. Hainsworth,et al.  Safety of bevacizumab plus chemotherapy as first-line treatment of patients with metastatic colorectal cancer: Updated results from a large observational registry in the US (BRiTE). , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[35]  R. Motzer,et al.  Sunitinib in patients with metastatic renal cell carcinoma. , 2006, JAMA.

[36]  B. Lane,et al.  Reversible posterior leukoencephalopathy syndrome and bevacizumab. , 2006, The New England journal of medicine.

[37]  S. Douma,et al.  Vascular Endothelial Growth Factor and Nitric Oxide Serum Levels in Arterial Hypertension , 2006, Clinical and experimental hypertension.

[38]  D. Cunningham,et al.  Managing Patients Treated with Bevacizumab Combination Therapy , 2005, Oncology.

[39]  R. Havlik,et al.  Age and comorbidity impact surgical therapy in older bladder carcinoma patients , 2005, Cancer.

[40]  T. Gustafsson,et al.  Antagonism of the renin-angiotensin system can counteract cardiac angiogenic vascular endothelial growth factor gene therapy and myocardial angiogenesis in the normal heart. , 2005, American journal of hypertension.

[41]  J. Rosiak,et al.  Hypertension associated with bevacizumab. , 2005, Clinical journal of oncology nursing.

[42]  G. Demetri,et al.  Phase 3, multicenter, randomized, double-blind, placebo-controlled trial of SU11248 in patients (pts) following failure of imatinib for metastatic GIST , 2005 .

[43]  J. Hainsworth,et al.  A randomized, double-blind, placebo-controlled, phase III study in patients (Pts) with metastatic adenocarcinoma of the colon or rectum receiving first-line chemotherapy with oxaliplatin/5-fluorouracil/leucovorin and PTK787/ZK 222584 or placebo (CONFIRM-1) , 2005 .

[44]  J. Berlin,et al.  Bevacizumab in combination with fluorouracil and leucovorin: an active regimen for first-line metastatic colorectal cancer. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[45]  S. Miura,et al.  Nifedipine-Induced Vascular Endothelial Growth Factor Secretion from Coronary Smooth Muscle Cells Promotes Endothelial Tube Formation via the Kinase Insert Domain-Containing Receptor/Fetal Liver Kinase-1/NO Pathway , 2005, Hypertension Research.

[46]  P Kelly Marcom,et al.  Randomized phase III trial of capecitabine compared with bevacizumab plus capecitabine in patients with previously treated metastatic breast cancer. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[47]  Kui Zhao,et al.  Changes of expressions of VEGF, bFGF, and angiogenesis, and effect of benazepril, bFGF on angiogenesis in acute myocardial infarction model of the rabbits. , 2004, Biomedical and environmental sciences : BES.

[48]  N. Day,et al.  Fat distribution, body mass index and blood pressure in 22 090 men and women in the Norfolk cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC-Norfolk) study , 2004, Journal of hypertension.

[49]  Tim Eisen,et al.  Kinase Inhibition with BAY 43–9006 in Renal Cell Carcinoma , 2004, Clinical Cancer Research.

[50]  K. Flaherty,et al.  Pharmacodynamic study of the raf kinase inhibitor BAY 43-9006: Mechanisms of hypertension. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[51]  J. Berlin,et al.  Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. , 2004, The New England journal of medicine.

[52]  Edward L Spitznagel,et al.  Prognostic importance of comorbidity in a hospital-based cancer registry. , 2004, JAMA.

[53]  Daniel W. Jones,et al.  Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. , 2003, Hypertension.

[54]  Seth M Steinberg,et al.  A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer. , 2003, The New England journal of medicine.

[55]  Daniel W. Jones,et al.  The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. , 2003, JAMA.

[56]  R. Kalluri,et al.  Neutralization of Circulating Vascular Endothelial Growth Factor (VEGF) by Anti-VEGF Antibodies and Soluble VEGF Receptor 1 (sFlt-1) Induces Proteinuria* , 2003, The Journal of Biological Chemistry.

[57]  Brian H Annex,et al.  The VIVA Trial Vascular Endothelial Growth Factor in Ischemia for Vascular Angiogenesis , 2003 .

[58]  R. Collins,et al.  Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies , 2002, The Lancet.

[59]  Ethan M Balk,et al.  K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. , 2002, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[60]  R. Poveda,et al.  Goodpasture syndrome during the course of a Schönlein-Henoch purpura. , 2002, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[61]  H. Granger,et al.  VEGF upregulates ecNOS message, protein, and NO production in human endothelial cells. , 1998, American journal of physiology. Heart and circulatory physiology.

[62]  J. Isner,et al.  Vascular endothelial growth factor/vascular permeability factor produces nitric oxide-dependent hypotension. Evidence for a maintenance role in quiescent adult endothelium. , 1997, Arteriosclerosis, thrombosis, and vascular biology.

[63]  G. Bray,et al.  A clinical trial of the effects of dietary patterns on blood pressure. DASH Collaborative Research Group. , 1997, The New England journal of medicine.

[64]  C. Ozcan,et al.  Reversible posterior leukoencephalopathy syndrome and bevacizumab. , 2006, The New England journal of medicine.

[65]  D. López,et al.  ACE inhibitors improve nephrin expression in Zucker rats with glomerulosclerosis. , 2005, Kidney international. Supplement.

[66]  D. Sane,et al.  Angiogenic growth factors and hypertension , 2004, Angiogenesis.

[67]  E. Agabiti-Rosei [Structural and functional changes of the microcirculation in hypertension: influence of pharmacological therapy]. , 2003, Drugs.

[68]  Enrico Agabiti-Rosei Modifications structurelles et fonctionnelles de la microcirculation dans l’hypertension: Influence du traitement pharmacologique , 2003 .

[69]  D. Adu,et al.  Knowledge of renal histology alters patient management in over 40% of cases. , 1994, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.