Eventos adversos cardiovasculares asociados a la terapia antineoplásica oral

Revisión integrativa de literatura en las bases de datos SCOPUS, Scientific Electronic Library Online (SciELO), Cumulative Index to Nursing and Allied Health Literature (CINAHL) y Medical Literature Analysis and Retrieval System Online (MEDLINE). Se utilizaron descriptores antineoplásicos, cardiotoxicidad, el sistema cardiovascular y reacción adversa en Portugués, Inglés y Español. Se seleccionaron 23 artículos publicados entre 1985 y 2015.

Resultados:

Veinte estudios estaban relacionados con los eventos cardiacos y once con los eventos vasculares periféricos. Los eventos adversos cardiacos más frecuentes fueron la disminución de la fracción de eyección del ventrículo izquierdo, infarto de miocardio, cambios en el electrocardiograma, insuficiencia cardíaca y angina, mientras que los vasculares periféricos fueron hipertensión arterial y tromboembolismo.

Conclusión:

La terapia antineoplásica oral está asociada a diferentes eventos adversos, entre ellos los cardíacos y los vasculares periféricos.

Descriptores:
Antineoplásicos; Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos; Cardiotoxicidad; Sistema Cardiovascular; Revisión

Title	Country/ Year	Design/Study sample	Outcome
The frequency and severity of cardiovascular toxicity from targeted therapy in advanced renal cell carcinoma patients ⁽ ¹¹11 Hall PS, Harshman LC, Srinivas S, Witteles RM. The frequency and severity of cardiovascular toxicity from targeted therapy in advanced renal cell carcinoma patients. JACC: Heart Fail[Internet]. 2013 [cited 2016 Oct 16]; 1(1):72-8. Available from: http://www.sciencedirect.com/science/article/pii/S2213177912000030 http://www.sciencedirect.com/science/art... ⁾	United States/ 2013	Cohort 289 patients with advanced renal cell carcinoma	- Sunitinib: heart failure (2%), coronary artery disease (9%) and atrial fibrillation (1%). - Sorafenib: heart failure (4%), coronary artery disease (5%) and atrial fibrillation (4%). - Pazopanib: heart failure (2%), coronary artery disease (2%) and atrial fibrillation (5%).
Cardiac toxicity of sunitinib and sorafenib in patients with metastatic renal cell carcinoma ⁽ ¹²12 Schmidinger M, Zielinski CC, Vogl UM, Bojic A, Bojic M, Schukro C, et al. Cardiac toxicity of sunitinib and sorafenib in patients with metastatic renal cell carcinoma. J Clin Oncol [Internet]. 2008 [cited 2016 Oct 16]; 26(32):5204-12. Available from: http://jco.ascopubs.org/content/26/32/5204.full.pdf+html http://jco.ascopubs.org/content/26/32/52... ⁾	United States, 2008	Cohort 86 patients with metastatic renal cell carcinoma	- Sunitinib or sorafenib: changes in electrocardiogram (46.5%), reduced left ventricular ejection fraction (10.4%); pericardial effusion (1%), rise in cardiac enzymes (30%).
Phase I and Pharmacokinetic Study of Sunitinib in Pediatric Patients with Refractory Solid Tumors: A Children's Oncology Group Study ⁽ ¹³13 DuBois SG, Shusterman S, Ingle AM, Ahern CH, Reid JM, Wu B, et al. Phase I and pharmacokinetic study of sunitinib in pediatric patients with refractory solid tumors: a children's oncology group study. Clin Cancer Res [Internet]. 2011 [cited 2016 Oct 16]; 17(15):5113-22. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3149978/pdf/nihms303199.pdf https://www.ncbi.nlm.nih.gov/pmc/article... ⁾	United States, 2010	Clinical trial 33 patients from 2 to 21 years old with refractory solid tumors	- Sunitinib: Left ventricular systolic dysfunction (8.6%), prolongation of QTc on the electrocardiogram (8.6%).
Hyperlipidemia and Hypothyroidism Among Metastatic Renal Cell Carcinoma Patients Taking Sunitinib Malate ⁽ ¹⁴14 Tassi R, Baldazzi V, Lapini A, Carini M, Mazzanti R. Hyperlipidemia and hypothyroidism among metastatic renal cell carcinoma patients taking sunitinib malate: related or unrelated adverse events? Clin Genitour Cancer[Internet]. 2015 [cited 2016 Oct 16]; 13(2):e101-5. Available from: http://www.clinical-genitourinary-cancer.com/article/S1558-7673(14)00202-X/pdf http://www.clinical-genitourinary-cancer... ⁾	United States, 2015	Cohort 39 patients with metastatic renal cell carcinoma	- Sunitinib: decrease of left ventricular function and death after myocardial infarction (2.5%).
Sunitinib versus Interferon Alfa in Metastatic Renal-Cell Carcinoma ⁽ ¹⁵15 Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Rixie O, et al. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med [Internet]. 2007 [cited 2016 Oct 16]; 356:115-24. Available from: http://www.nejm.org/doi/pdf/10.1056/NEJMoa065044 http://www.nejm.org/doi/pdf/10.1056/NEJM... ⁾	United States, 2007	Clinical trial 750 patients with metastatic renal cell carcinoma	- Sunitinib: reduced left ventricular ejection fraction (2%).- Interferon alfa: decrease of left ventricular ejection fraction (1%).
Rare Incidence of Congestive Heart Failure in Gastrointestinal Stromal Tumor and Other Sarcoma Patients Receiving Imatinib Mesylate (IM) ⁽ ¹⁶16 Trent JC, Patel SS, Zhang J, Araujo DM, Plana J, Lenihan DJ, et al. Rare incidence of congestive heart failure in gastrointestinal stromal tumor and other sarcoma patients receiving Imatinib Mesylate (IM). Cancer [Internet]. 2010 [cited 2016 Oct 16]; 116(1):184-92. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4306337/pdf/nihms149947.pdf https://www.ncbi.nlm.nih.gov/pmc/article... ⁾	United States, 2010	Cohort 219 patients with sarcoma	- Imatinibe: myocardial ischemia or chest pain (2.3%), arrhythmias (0.9%); alterations in the electrocardiogram (1%), left ventricular dysfunction (0.4%), cardiac arrest (0.4%), heart failure (0.5%).
Randomized study of lapatinib alone or in combination with trastuzumab in women with ErbB2-positive, trastuzumab-refractory metastatic breast cancer ⁽ ¹⁷17 Blackwell KL, Burstein HJ, Storniolo AM, Rugo H, Sledge G, Koehler M, et al. Randomized study of lapatinib alone or in combination with trastuzumab in women with ErbB2-Positive, Trastuzumab-Refractory Metastatic Breast Cancer. J Clin Oncol [Internet]. 2010 [cited 2016 Oct 16]; 28:1124-30. Available from: http://jco.ascopubs.org/content/28/7/1124.full.pdf+html http://jco.ascopubs.org/content/28/7/112... ⁾	United States, 2010	Clinical trial 296 women with ErbB2-positive metastatic breast cancer	- Lapatinib: reduced left ventricular ejection fraction (2%).
Phase 1 Pharmacokinetic and Drug-Interaction Study of Dasatinib in Patients With Advanced Solid Tumors ⁽ ¹⁹19 Johnson FM, Agrawal S, Burris H, Rosen L, Dhillon N, Hong D, et al. Phase 1 pharmacokinetic and drug-interaction study of Dasatinib in patients with advanced solid tumors. Cancer [Internet]. 2010 [cited 2016 Oct 16]; 116:1582-91. Available from: http://onlinelibrary.wiley.com/doi/10.1002/cncr.24927/pdf http://onlinelibrary.wiley.com/doi/10.10... ⁾	United States, 2010	Clinical trial 29 patients with advanced solid tumors	- Dasatinib: QTc interval prolongation on the electrocardiogram (3.5%).
A Prospective Randomized Trial of Doxorubicin Versus ldarubicin in the Treatment of Advanced Breast Cancer ⁽ ²⁰20 Lopez M, Contegiacomo A, Vici P, Ioio CD, Lauro L, Pagliarulo C, et al. A prospective randomized trial of Doxorubicin versus ldarubicin in the treatment of advanced breast cancer. Cancer [Internet]. 1989 [cited 2016 Oct 16]; 64:2431-6. Available from: http://onlinelibrary.wiley.com/doi/10.1002/1097-0142(19891215)64:12%3C2431::AID-CNCR2820641206%3E3.0.CO;2-1/pdf http://onlinelibrary.wiley.com/doi/10.10... ⁾	United States, 1989	Clinical trial 76 patients with advanced breast cancer	- Idarubicin: reduced left ventricular ejection fraction (5.8%)
Phase I Clinical Trial of Orally Administered 4-Demethoxydaunorubicin (Idarubicin) with Pharmacokinetic and in Vitro Drug Sensitivity Testing in Children with Refractory Leukemia ⁽ ²¹21 Pui C, Graaf SSN, Dow LW, Rodman JH, Evans WE, Alpert BS, et al. Phase I clinical trial of orally administered 4- Demethoxydaunorubicin (Idarubicin ) with pharmacokinetic and in vitro drug sensitivity testing in children with refractory leukemia. Cancer Res [Internet]. 1988 [cited 2016 Oct 16]; 48:5348-52. Available from: http://cancerres.aacrjournals.org/content/48/18/5348.full-text.pdf http://cancerres.aacrjournals.org/conten... ⁾	United States, 1988	Clinical trial 15 children with acute refractory leukemia	- Idarubicin: reduced left ventricular ejection fraction (6.6%) and of fractional shortening (40%).
Capecitabine, an Oral Fluoropyrimidine Carbamate With Substantial Activity in Advanced Colorectal Cancer: Results of a Randomized Phase II Study ⁽ ²²22 Cutsem EV, Findlay M, Osterwalder B, Kocha W, Dalley D, Pazdur R, et al, Capecitabine, an oral fluoropyrimidine carbamate with substantial activity in advanced colorectal cancer: results of a randomized phase ii study. J Clin Oncol [Internet]. 2000 Mar [cited 2016 Oct 16]; 18(6): 1337-45. Available from: https://www.ncbi.nlm.nih.gov/pubmed/10715306 https://www.ncbi.nlm.nih.gov/pubmed/1071... ⁾	United States, 2000	Clinical trial 109 patients with advanced colorectal cancer	- Capecitabine: Angina (1.8%), atrial fibrillation (0.9%) and chest pain (2.7%).
Cardiotoxicity associated with the cancer therapeutic agent sunitinib malate ⁽ ²⁴24 Telli ML, Witteles RM, Fisher GA, Srinivas S. Cardiotoxicity associated with the cancer therapeutic agent sunitinib malate. Ann Oncol [Internet]. 2008 [cited 2016 Oct 16]; 19:1613-8. Available from: http://annonc.oxfordjournals.org/content/19/9/1613.full.pdf+html http://annonc.oxfordjournals.org/content... ⁾	England, 2008	Cohort 48 patients with renal cell cancer or gastrointestinal stromal tumor	- Sunitinib: ventricular dysfunction with the reduced left ventricular ejection fraction (12.5%) and cardiogenic shock (2%).
Cardiotoxicity Associated with the Tyrosine Kinase Inhibitor Sunitinib ⁽ ²⁵25 Chu TF, Rupnick MA, Kerkela R, Dallabrida SM, Zurakowski D, Nguyen L, et al. Cardiotoxicity associated with the Tyrosine Kinase Inhibitor Sunitinib. Lancet [Internet]. 2007 [cited 2016 Oct 16]; 370(9604):2011-9. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2643085/pdf/nihms37146.pdf https://www.ncbi.nlm.nih.gov/pmc/article... ⁾	England, 2007	Cohort 75 patients with imatinib resistant gastrointestinal stromal tumor	- Sunitinib: congestive heart failure (8%), reduced left ventricular ejection fraction (28%), rise in troponin (18%) and death after myocardial infarction (1.3%).
Cardiovascular toxicity following sunitinib therapy in metastatic renal cell carcinoma: a multicenter analysis ⁽ ²⁶26 Lorenzo G, Autorino R, Bruni G, Carteni G, Ricevuto E, Tudini M, et al. Cardiovascular toxicity following sunitinib therapy in metastatic renal cell carcinoma: a multicenter analysis. Ann Oncol [Internet]. 2009 [cited 2016 Oct 16]; 20:1535-42. Available from: http://annonc.oxfordjournals.org/content/20/9/1535.full.pdf+html http://annonc.oxfordjournals.org/content... ⁾	England, 2009	Cohort 175 patients with metastatic renal cell carcinoma	- Sunitinib: reduced left ventricular ejection fraction (18.9%) and congestive heart failure (6.9%).
QTc interval prolongation with vascular endothelial growth factor receptor tyrosine kinase inhibitors ⁽ ²⁷27 Ghatalia P, Je Y, Kaymakcalan MD, Sonpavde G, Choueiri TK. QTc interval prolongation with vascular endothelial growth factor receptor tyrosine kinase inhibitors. British J Cancer [Internet]. 2015 [cited 2016 Oct 16]; 112(2):296-305. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4453446/pdf/bjc2014564a.pdf https://www.ncbi.nlm.nih.gov/pmc/article... ⁾	England, 2015	Metanalysis 6548 patients with hepatocellular carcinoma, soft tissue sarcoma, renal cell carcinoma, colorectal, prostate, pancreatic, breast, thyroid, lung or gallbladder cancer	- Tyrosine kinase inhibitors in general: changes in electrocardiogram (4.4%, RR= 66, CI= 95% and p=0.001 in relation to other antineoplastic agents). - Axitinib: ventricular tachycardia (0.33%). - Capecitabine: Atrial fibrillation (0.93%). - Vandetanib: Atrial fibrillation (0.56%), ventricular tachycardia (1.37%) and cardiac arrest (0.15%). - Pazopanib: atrial fibrillation (0.37%) and cardiac arrest (0.34%).
Comprehensive side-eff ect profi le of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: long-term safety analysis of the ATAC trial ⁽ ²⁹29 The Arimidex, Tamoxifen, Alone or in combination Trialists' Group. Buzdar A, Howell A, Cuzick J, Wale C, Distler W, Hoctin-Boes G, et al. Comprehensive side-effect profile of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: long-term safety analysis of the ATAC trial. Lancet Oncol [Internet]. 2006 [cited 2016 Oct 16]; 7:633-43. Available from: http://www.thelancet.com/pdfs/journals/lanonc/PIIS1470-2045(06)70767-7.pdf http://www.thelancet.com/pdfs/journals/l... ⁾	England, 2006	Clinical trial 6241 women after menopause with breast cancer	- Anastrozole: angina, myocardial infarction, myocardial ischemia and coronary artery disease (2%). - Tamoxifeno: Angina, myocardial ischemia and coronary artery disease (2%) and myocardial infarction (1%).
Activity of 4 Demethoxydaunorubicin by the Oral Route in Advanced Breast Cancer ⁽ ³⁰30 Martoni A, Pacciarini MA, Pannuti F. Activity of 4-Demethoxydaunorubicin by the Oral Route in Advanced Breast Cancer. Eur J Cancer Clin Oncol [Internet]. 1985 Jul [cited 2016 Oct 16]; 21(7): 803-6. Available from: https://www.ncbi.nlm.nih.gov/pubmed/3862582 https://www.ncbi.nlm.nih.gov/pubmed/3862... ⁾		Clinical trial 29 patients with advanced breast cancer	- Idarrubicina: Changes in electrocardiogram (6.8%) and reduced left ventricular ejection fraction (3.4%).
A randomized, double-blind, placebo-controlled study to evaluate the effect of repeated oral doses of pazopanib on cardiac conduction in patients with solid tumors ⁽ ³¹31 Heath EI, Infante J, Lewis LD, Luu T, Stephenson J, Tan AR, et al. A randomized, double-blind, placebo-controlled study to evaluate the effect of repeated oral doses of pazopanib on cardiac conduction in patients with solid tumors. Cancer Chemother Pharmacol [Internet]. 2013 [cited 2016 Oct 16]; 71(3):565-73. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3899892/pdf/nihms-516601.pdf https://www.ncbi.nlm.nih.gov/pmc/article... ⁾	Germany, 2013	Clinical trial95 patients with advanced solid tumors	- Pazopanib: decreased heart rate (mean= 9.9 bpm), prolongation of 4.4 ms in the QTc interval (90 % CI: -2.4, 11.2), compared to placebo.
Clinical cardiac safety profile of nilotinib ⁽ ³²32 Kim TD, Coutre P, Schwarz M, Grille P, Levitin M, Fateh-Moghadam S, et al. Clinical cardiac safety profile of nilotinib. Haematol [Internet]. 2012 [cited 2016 Oct 16]; 97(6):883-9. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3366654/pdf/0970883.pdf https://www.ncbi.nlm.nih.gov/pmc/article... ⁾	Italy, 2012	Cohort 81 patients previously treated with nilotinib	- Nilotinib: Myocardial infarction (2.4%), acute coronary syndrome (7.4%), atrial fibrillation (1.2%), angina (1.2%) and changes in electrocardiogram (20%).
Increased prevalence of subclinical cardiac valve fibrosis in patients with prolactinomas on long-term bromocriptine and cabergoline treatment ⁽ ³³33 Elenkova A, Shabani R, Kalinov K, Zacharieva S. Increased prevalence of subclinical cardiac valve fibrosis in patients with prolactinomas on long-term bromocriptine and cabergoline treatment. European J Endocrinol [Internet]. 2012 [cited 2016 Oct 16]; 167(1):17-25. Available from: http://www.eje-online.org/content/167/1/17.full.pdf+html http://www.eje-online.org/content/167/1/... ⁾	Norway, 2012	Case-control 334 patients with prolactinoma	- Cabergoline: Asymptomatic pericardial effusion (0.9%) and risk of cardiac fibrosis (OR=2.27, p= 0.016). - Bromocriptine: Asymptomatic pericardial effusion (1.8%) and risk of cardiac fibrosis (OR=2.66, p= 0.014).

Title	Year/Country	Design/Study sample	Outcome
The frequency and severity of cardiovascular toxicity from targeted therapy in advanced renal cell carcinoma patients ⁽ ¹¹11 Hall PS, Harshman LC, Srinivas S, Witteles RM. The frequency and severity of cardiovascular toxicity from targeted therapy in advanced renal cell carcinoma patients. JACC: Heart Fail[Internet]. 2013 [cited 2016 Oct 16]; 1(1):72-8. Available from: http://www.sciencedirect.com/science/article/pii/S2213177912000030 http://www.sciencedirect.com/science/art... ⁾	United States, 2013	Cohort 289 patients with advanced renal cell carcinoma	- Sunutinib: hypertension (44%). - Sorafenib: hypertension (52%). - Pazopanib: hypertension (49%).
Cardiac Toxicity of Sunitinib and Sorafenib in Patients With Metastatic Renal Cell Carcinoma ⁽ ¹²12 Schmidinger M, Zielinski CC, Vogl UM, Bojic A, Bojic M, Schukro C, et al. Cardiac toxicity of sunitinib and sorafenib in patients with metastatic renal cell carcinoma. J Clin Oncol [Internet]. 2008 [cited 2016 Oct 16]; 26(32):5204-12. Available from: http://jco.ascopubs.org/content/26/32/5204.full.pdf+html http://jco.ascopubs.org/content/26/32/52... ⁾	United States, 2008	Cohort 86 patients with metstatic renal cell carcinoma	- Sunitinib or sorafenib: ischemic optic neuropathy and occlusion of the posterior tibial artery (1%).
Phase I and Pharmacokinetic Study of Sunitinib in Pediatric Patients with Refractory Solid Tumors: A Children's Oncology Group Study ⁽ ¹³13 DuBois SG, Shusterman S, Ingle AM, Ahern CH, Reid JM, Wu B, et al. Phase I and pharmacokinetic study of sunitinib in pediatric patients with refractory solid tumors: a children's oncology group study. Clin Cancer Res [Internet]. 2011 [cited 2016 Oct 16]; 17(15):5113-22. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3149978/pdf/nihms303199.pdf https://www.ncbi.nlm.nih.gov/pmc/article... ⁾	United States, 2010	Clinical trial 33 patients de 2 a 21 anos, com refractory solid tumors	- Sunitinib: hypertension (12%).
Sunitinib versus Interferon Alfa in Metastatic Renal-Cell Carcinoma ⁽ ¹⁵15 Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Rixie O, et al. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med [Internet]. 2007 [cited 2016 Oct 16]; 356:115-24. Available from: http://www.nejm.org/doi/pdf/10.1056/NEJMoa065044 http://www.nejm.org/doi/pdf/10.1056/NEJM... ⁾	United States, 2007	Clinical trial 750 patients with carcinoma de célula renal metastático	- Sunitinib: hypertension (8%).
Hypertension and Rarefaction during Treatment with Telatinib, a Small Molecule Angiogenesis Inhibitor⁽¹⁸18 Steeghs N, Gelderblom H, Roodt J, Christensen O, Rajagopalan P, Hovens M. Hypertension and rarefaction during treatment with Telatinib, a small molecule angiogenesis inhibitor. Clin Cancer Res [Internet]. 2008 [cited 2016 Oct 16]; 14(11):3470-7. Available from: http://clincancerres.aacrjournals.org/content/14/11/3470.full-text.pdf http://clincancerres.aacrjournals.org/co... ⁾	United States, 2008	Clinical trial 18 patients with solid tumors	- Telatinib: rise in blood pressure (78%); (aortic pulse wave velocity increased in 94% of patients, p=0.001), decreased skeletal muscle capillary density and decreased blood flow in the skin (p=0.015).
Oral Melphalan, Prednisone, and Thalidomide for Newly Diagnosed Patients with Myeloma⁽²³23 Palumbo A, Bertola A, Musto P, Caravita T, Callea V, Nunzi M et al. Oral Melphalan, Prednisone, and Thalidomide for newly diagnosed patients with myeloma. Cancer [Internet]. 2005 [cited 2016 Oct 16]; 104:1428-33. Available from: http://onlinelibrary.wiley.com/doi/10.1002/cncr.21342/pdf http://onlinelibrary.wiley.com/doi/10.10... ⁾	United States, 2005	Clinical trial 41 patients with multiple myeloma	- Melphalan + Prednisone + thalidomide: thromboembolic Events (20%).
Cardiovascular toxicity Associated with the Tyrosine Kinase Inhibitor Sunitinib⁽²⁵25 Chu TF, Rupnick MA, Kerkela R, Dallabrida SM, Zurakowski D, Nguyen L, et al. Cardiotoxicity associated with the Tyrosine Kinase Inhibitor Sunitinib. Lancet [Internet]. 2007 [cited 2016 Oct 16]; 370(9604):2011-9. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2643085/pdf/nihms37146.pdf https://www.ncbi.nlm.nih.gov/pmc/article... ⁾	England, 2007	Cohort 75 patients with imatinib resistant gastrointestinal stromal tumor	- Sunitinib: hypertension (47%).
Cardiovascular toxicity following sunitinib therapy in metastatic renal cell carcinoma: a multicenter analysis ⁽ ²⁶26 Lorenzo G, Autorino R, Bruni G, Carteni G, Ricevuto E, Tudini M, et al. Cardiovascular toxicity following sunitinib therapy in metastatic renal cell carcinoma: a multicenter analysis. Ann Oncol [Internet]. 2009 [cited 2016 Oct 16]; 20:1535-42. Available from: http://annonc.oxfordjournals.org/content/20/9/1535.full.pdf+html http://annonc.oxfordjournals.org/content... ⁾	England, 2009	Cohort 175 patients with metastatic cell carcinoma	-Sunitinib: hypertension (13.7%).
Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial ⁽ ²⁸28 Demetri GD, Oosterom ATV, Garrett CR, Blackstein ME, Shah MH, Verweij J. Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib : a randomised controlled trial. Lancet [Internet]. 2006 [cited 2016 Oct 16]; 368(9544):1329-38. Available from: http://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(06)69446-4.pdf http://www.thelancet.com/pdfs/journals/l... ⁾	England, 2006	Clinical trial 312 patients with imatinib resistant gastrointestinal stromal tumor	- Sunitinib: hypertension (11%).
Comprehensive side-eff ect profi le of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: long-term safety analysis of the ATAC trial ⁽ ²⁹29 The Arimidex, Tamoxifen, Alone or in combination Trialists' Group. Buzdar A, Howell A, Cuzick J, Wale C, Distler W, Hoctin-Boes G, et al. Comprehensive side-effect profile of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: long-term safety analysis of the ATAC trial. Lancet Oncol [Internet]. 2006 [cited 2016 Oct 16]; 7:633-43. Available from: http://www.thelancet.com/pdfs/journals/lanonc/PIIS1470-2045(06)70767-7.pdf http://www.thelancet.com/pdfs/journals/l... ⁾	England, 2006	Clinical trial 6241 women after menopause with breast cancer	- Anastrozole: venous thromboembolic events (3%) and hypertension (13%). - Tamoxifen: thromboembolic venous events and hypertension (11%).
A randomized, double-blind, placebo-controlled study to evaluate the effect of repeated oral doses of pazopanib on cardiac conduction in patients with solid tumors ⁽ ³¹31 Heath EI, Infante J, Lewis LD, Luu T, Stephenson J, Tan AR, et al. A randomized, double-blind, placebo-controlled study to evaluate the effect of repeated oral doses of pazopanib on cardiac conduction in patients with solid tumors. Cancer Chemother Pharmacol [Internet]. 2013 [cited 2016 Oct 16]; 71(3):565-73. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3899892/pdf/nihms-516601.pdf https://www.ncbi.nlm.nih.gov/pmc/article... ⁾	Germany, 2013	Clinical trial 95 patients with advanced solid tumors	- Pazopanib: Transient increase in systolic blood pressure (mean +17.7 mmHg, SD=14.2) and diastolic (mean +11.9 mmHg, SD=6.3) and hypertension (15%).

Associação Brasileira de Enfermagem SGA Norte Quadra 603 Conj. "B" - Av. L2 Norte 70830-102 Brasília, DF, Brasil, Tel.: (55 61) 3226-0653, Fax: (55 61) 3225-4473 - Brasília - DF - Brazil
E-mail: reben@abennacional.org.br

Acompanhe os números deste periódico no seu leitor de RSS

[1] CORRESPONDING AUTHOR: Jacqueline Mota da Silva. E-mail: jacque18ms@gmail.com