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Complications cardiaques et vasculaires des antiangiogéniques (à l’exception des effets rénaux et des complications hémorragiques)

Vascular and cardiac complications of angiogenesis inhibitors (excluding renal effects and hemorrhagic complications)

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Oncologie

Abstract

The antiangiogenic agents are now part of themanagement of many solid tumors. They are commonly used in the treatment of digestive, kidney, breast, and lung carcinomas. Adverse events are better identified, taken into account, and managed. Of these, hypertension is the most common during the first weeks of treatment. In addition to lifestyle changes, it often requires the use of a specific treatment, which usually allows the treatment to be continued. The occurrences of thromboembolic events, especially arterial ones, are not uncommon. Better selection of patients at risk according tomedical history and underlying illness can prevent the occurrence of fatal events. The impact of antiangiogenic agents on cardiac function (isolated decrease of ejection fraction or symptomatic heart failure), though less frequent with other targeted therapies (like anti-HER2 therapies) still requires an initial assessment and regular follow-up, especially in patients with cardiac risk factors. The management of these toxicities is important to be known, and adverse reactions of such drugs should be measured and weighed against the beneficial effects expected.

Résumé

Les antiangiogéniques intraveineux ou oraux font désormais partie intégrante de la prise en charge de nombreuses tumeurs solides. Les données les plus matures concernent les cancers digestifs, du rein, du sein et bronchiques. Les toxicités spécifiques sont de mieux en mieux individualisées et prises en charge. Parmi celles-ci, l’hypertension artérielle est l’une des plus fréquentes au cours des premières semaines de traitement. En plus des mesures hygiénodiététiques, elle nécessite souvent le recours à un traitement spécifique qui permet le plus souvent la poursuite des antiangiogéniques. Les accidents thromboemboliques, surtout artériels, ont une incidence non négligeable. Une meilleure sélection des patients à risque en fonction des antécédents ou du type de cancer peut permettre d’éviter la mise en jeu du pronostic vital. Le retentissement sur la fonction cardiaque (baisse isolée de la fraction d’éjection ou insuffisance cardiaque symptomatique), s’il est moindre avec les thérapeutiques ciblant la voie EGFR, nécessite tout de même une évaluation initiale et régulière au cours du suivi, notamment chez les patients à risque. La gestion de ces toxicités est donc importante à connaître, et dans tous les cas, il faudra évaluer la balance bénéfices/risques.

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Références

  1. Aghajanian C, Finkler NJ, Rutherford T, et al. (2011) OCEANS: a randomized, doubleblinded, placebo-controlled phase III trial of chemotherapy with or without bevacizumab (BEV) in patients with platinumsensitive recurrent epithelial ovarian (EOC), primary peritoneal (PPC), or fallopian tube cancer (FTC). J Clin Oncol 29: (suppl; abstr LBA5007)

  2. Azizi M, Chedid A, Oudard S (2008) Home blood-pressure monitoring in patients receiving sunitinib. N Engl J Med 3: 95–97

    Article  Google Scholar 

  3. Chen Helen X, Cleck Jessica N (2009) Adverse effects of anticancer agents that target the VEGF pathway. J N Nat Rev Clin Oncol 94: 1–13

    Google Scholar 

  4. Chobanian AV, Bakris GL, Black HR, et al. (2003) Seven report of the Joint National Committee on prevention, detection, evaluation and treatment of high blood pressure. Hypertension 42: 1206–1252

    Article  PubMed  CAS  Google Scholar 

  5. Choueiri TK, Schutz FAB, Jé Y, et al. (2010) Risk of thromboembolic events with sunitinib and sorafenib: a systematic review and meta-analysis of clinical trials. J Clin Oncol 13: 2280–2285

    Article  Google Scholar 

  6. Choueiri TK, Mayer EL, Je Y, et al. (2011) Congestive heart failure risk in patients with breast cancer treated with bevacizumab. J Clin Oncol 28: 1–7

    Google Scholar 

  7. Chu TF, Rupnick MA, Kerkela R, et al. (2007) Cardiotoxicity associated with tyrosine-kinase inhibitor sunitinib. Lancet 370: 2011–2019

    Article  PubMed  CAS  Google Scholar 

  8. Dahlberg SE, Sandler AB, Brahmer JR, et al. (2010) Clinical course of advanced non-small-cell lung cancer patients experiencing hypertension during treatment with bevacizumab in combination with carboplatin and paclitaxel on ECOG4599. J Clin Oncol 28: 949–954

    Article  PubMed  CAS  Google Scholar 

  9. Demetri GD, Van Oosterom AT, Garrett CR, et al. (2006) Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial. Lancet 368: 1329–1338

    Article  PubMed  CAS  Google Scholar 

  10. Ederhy S Izzedine H Massard C et al. (2011) Cardiac side effects of molecular targeted therapies: toward a better dialogue between oncologists and cardiologist. Crit Rev Oncol Hematol 80: 369–379

    Article  PubMed  Google Scholar 

  11. Ederhy S, Duclos B, Mahammedi H, et al. (2011) Gestion des effets secondaires des thérapies ciblées dans le cancer du rein: effets secondaires cardiovasculaires. Bull Cancer 98: S19–S34

    Google Scholar 

  12. Eisen T, Sternberg CN, Robert C, et al. (2011) Targeted Therapies for Renal Cell Carcinoma: Review of Adverse Event Management Strategies. JNCI 104: 93–113

    Google Scholar 

  13. Escudier B, Pluzanska A, Koralewski P, et al. (2007) Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, doubleblind phase III trial. Lancet 370: 2103–2111

    Article  PubMed  Google Scholar 

  14. Escudier B, Eisen T, Stadler WM, et al. (2007) Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med 356: 125–134

    Article  PubMed  CAS  Google Scholar 

  15. Ewer MS, Vooletich MT, Durand JB, et al. (2005) Reversibility of trastuzumab related cardiotoxicity: new insights based on clinical course and response to medical treatment. J Clin Oncol 23: 7820–7826

    Article  PubMed  CAS  Google Scholar 

  16. Giantonio BJ, Catalano PJ, Meropol NJ, et al. (2007) Bevacizumab in combination with oxaliplatin, fluorouracile and leucovorin (folfox4) for previously treated metastatic colorectal cancer: results from the Eastern Cooperatvie Oncology Group study E3200. J Clin Oncol 25: 1539–1544

    Article  PubMed  CAS  Google Scholar 

  17. Giordano FJ, Gerber HP, Williams SP, et al. (2001) A cardiac myocyte vascular endothelial growth factor paracrine pathway is required to maintain cardiac function. Proc Natl Acad USA 98: 5780–5785

    Article  CAS  Google Scholar 

  18. Gollob JA, Rathmell WK, Richmond TM, et al. (2007) Phase II trial of sorafenib plus interferon alfa-2b as first- or second-line therapy in patients with metastatic renal cell cancer. J Clin Oncol 25: 3288–3295

    Article  PubMed  CAS  Google Scholar 

  19. Halimi JM, Azizi M, Bobrie G, et al. (2008) Effets vasculaires et rénaux des médicaments antiangiogéniques: recommandations françaises pour la pratique (SN, SFHTA, APNET, FFCD). Nephrol Ther 4: 602–615

    Article  PubMed  Google Scholar 

  20. Hecht JR, Trarbach T, Jaegger E, et al. (2005) 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). J Clin Oncol 23(Suppl): S1090A abs 3

    Google Scholar 

  21. Henry TD, Annex BH, McKendall GR et al. (2003) The Viva trial: vascular endothelial growth factor in ischemia for vascular angiogenesis. Circulation 107: 1359–1365

    Article  PubMed  CAS  Google Scholar 

  22. Hurwitz H, Fehrenbacher L, Novotny W, et al. (2004) Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 350: 2335–2342

    Article  PubMed  CAS  Google Scholar 

  23. Hutson TE, Davis ID, Machiels JP, et al. (2007) Pazopanib (GW786034) is active in metastatic renal cell carcinoma: interim results of a phase II randomized discontinuation trial [meeting abstracts]. J Clin Oncol 25(18 Suppl): 5031

    Google Scholar 

  24. Izzedine H, Ederhy S, Goldwasser F, et al. (2009) Management of hypertension in angiogenesis inhibitor-treated patients. Ann Oncol 20: 807–815

    Article  PubMed  CAS  Google Scholar 

  25. Jessup M, Abraham WT, Casey DE, et al. (2009) 2009 focused update: ACCF/AHA guidelines for the diagnosis and management of heart failure in adults: a report of The American College of Cardiology Foundation/American Task Force on Practice Guidelines: developed in collaboration with the International Society for Heart and Lung Transplantation. Circulation 119: 1977–2016

    Article  PubMed  Google Scholar 

  26. Kamba T, McDonald DM (2007) Mecanisms of adverse effects of anti-VEGF therapy for cancer. Br J Cancer 96: 1788–1795

    Article  PubMed  CAS  Google Scholar 

  27. Kozloff M, Yood MU, Berlin J, et al. (2009) Clinical outcomes associated with bevacizumab-containing treatment of metastatic colorectal cancer: The BRITE observational cohort study. Oncologist 14: 862–870

    Article  PubMed  CAS  Google Scholar 

  28. Langenberg MH, van Herpen CM, De Bono J, et al. (2009) Effective strategies for management of hypertension after vascular endothelial growth factor signaling inhibition therapy: results from a phase II randomized, factorial, double-blind study of cediranib in patients with advanced solid tumors. J Clin Oncol 27: 6152–6159

    Article  PubMed  CAS  Google Scholar 

  29. Levy BI (2006) Microvascular plasticity and experimental heart failure. Hypertension 47: 827–829

    Article  PubMed  CAS  Google Scholar 

  30. Llovet JM, Ricci S, Mazzaferro V, et al. (2008) Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 359: 378–390

    Article  PubMed  CAS  Google Scholar 

  31. Maitland ML, George L. Bakris GL, et al. (2010) Initial assessment, surveillance, and management of blood pressure in patients receiving vascular endothelial growth factor signaling pathway inhibitors. J Natl Cancer Inst 102: 1–9

    Article  Google Scholar 

  32. Miller KD, Chap LI, Holmes FA, et al. (2005) Randomized phase III trial of capecitabine compared with bevacizumab plus capecitabine in patients with previously treated metastatic breast cancer. J Clin Oncol 23: 792–799

    Article  PubMed  CAS  Google Scholar 

  33. Miller K, Wang M, Gralow J, et al. (2007) Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med 357: 2666–2676

    Article  PubMed  CAS  Google Scholar 

  34. Motzer RJ, Rini BI, Bukowski RM, et al. (2006) Sunitinib in patients with metastatic renal cell carcinoma. JAMA 295: 2516–2524

    Article  PubMed  CAS  Google Scholar 

  35. Motzer RJ, Hutson TE, Tomczak P, et al. (2007) Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med 356: 115–124

    Article  PubMed  CAS  Google Scholar 

  36. Mourad JJ, des Guetz G, Debbabi H, et al. (2008) Blood pressure rise following angiogenesis inhibition by bevacizumab. A crucial role for microcirculation. Ann Oncol 19: 927–934

    Article  PubMed  Google Scholar 

  37. Nalluri SR, Chu D, Keresztes R, et al. (2008) Risk of venous thromboembolism with the angiogenesis inhibitor bevacizumab in cancer patients. JAMA 300: 2277–2285

    Article  PubMed  CAS  Google Scholar 

  38. Noble S, Pasi J (2010) Epidemiology and pathophysiology of cancer-associated thrombosis. Br J Cancer 102(Suppl 1): S2–S9

    Article  PubMed  Google Scholar 

  39. Porta C, Szczylik C, Bracarda S, et al. (2008) Shortand long-term safety with sunitinib in an expanded access trial in metastatic renal cell carcinoma (mRCC). J Clin Oncol 26: 278s (suppl; abstr 5114)

    Google Scholar 

  40. Ranpura V, Pulipati B, Chu D, et al. (2010) Increased risk of high-grade hypertension with bevacizumab in cancer patients: a meta-analysis. Am J Hypertens 23: 460–468

    Article  PubMed  CAS  Google Scholar 

  41. Ranpura V, Hapani S, Wu S (2011) Treatment-related mortality with bevacizumab in cancer patients. JAMA 305: 487–494

    Article  PubMed  CAS  Google Scholar 

  42. Robinson ES, Matulonis UA, Ivy P, et al. (2010) Rapid development of hypertension and proteinuria with cediranib, an oral vascular endothelial growth factor receptor inhibitor. Clin J Am Soc Nephrol 5(3): 477–483

    Article  PubMed  CAS  Google Scholar 

  43. Rugo HS, Stopeck A, Joy AA, et al. (2007) A randomized, double-blind phase II study of the oral tyrosine-kinase inhibitor axitinib (AG-013736) in combination with docetaxel compared to docetaxel plus placebo in metastatic breast cancer [meeting abstracts]. J Clin Oncol 25(18 Suppl): 1003

    Google Scholar 

  44. Sandler A, Gray R, Perry MC, et al. (2006) Paclitaxel-carboplatin alone or with bevacizumab for non small cell lung cancer. NEJM 355: 2542–2550

    Article  PubMed  CAS  Google Scholar 

  45. Scappaticci FA, Skillings JR, Holden SN, et al. (2007) Arterial thromboembolic events in patients with metastatic carcinoma treated with chemotherapy and bevacizumab. J Natl Cancer Inst 99: 1232–1239

    Article  PubMed  Google Scholar 

  46. Schmidinger M, Zielinski CC, Vogl UM, et al. (2008) Cardiac toxicity of Sunitinb and Sorafenib in patients with metastatic renal cell carcinoma. J Clin Oncol 26: 5204–5212

    Article  PubMed  Google Scholar 

  47. Tan BY, Wei K, Rudge JS, et al. (2006) VEGF modulates erythropoietin through regulation of adult hepatic erythropoietin synthesis. Nat Med 12: 793–800

    Article  Google Scholar 

  48. Van Custem E, Rivera F, Berry S, et al. (2009) Safety and efficacy of first-line bevacizumab with FOLFOX, XELOX, FOLFIRI and fluoropyrimidines in metastatic colorectal cancer. The BEAT Study. Ann Oncol 20: 1842–1847

    Google Scholar 

  49. Yang JC, Haworth L, Sherry R, et al. (2003) A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer. N Engl J Med 349: 427–434

    Article  PubMed  CAS  Google Scholar 

  50. Zhu X, Wu S, Dahut WL, et al. (2007) Risks of proteinuria and hypertension with bevacizumab, an antibody against vascular endothelial growth factor: systematic review and meta-analysis. Am J Kidney Dis 49: 186–193

    Article  PubMed  CAS  Google Scholar 

Référence électronique

  1. NCI Common toxicity criteria. (2003) Version 3. www.ctep.cancer.gov

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  1. institut Sainte-Catherine, Unité de sénologie, 1750, chemin du Lavarin, F-84000, Avignon, France

    J. Grenier

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Grenier, J. Complications cardiaques et vasculaires des antiangiogéniques (à l’exception des effets rénaux et des complications hémorragiques). Oncologie 14, 237–247 (2012). https://doi.org/10.1007/s10269-012-2145-x

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  • DOI: https://doi.org/10.1007/s10269-012-2145-x

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