Eventos adversos cardiovasculares associados à terapia antineoplásica oral

Revisão integrativa de literatura nas bases de dados SCOPUS, Scientific Electronic Library Online (SciELO), Cumulative Index to Nursing and Allied Health Literature (CINAHL) e Medical Literature Analysis and Retrieval System Online (MEDLINE). Utilizaram-se os descritores antineoplásicos, cardiotoxicidade, sistema cardiovascular e reação adversa, em português, inglês e espanhol. Foram selecionados 23 artigos publicados entre 1985 e 2015.

Resultados:

Vinte estudos estavam relacionados aos eventos cardíacos e onze aos eventos vasculares periféricos. Os eventos adversos cardíacos mais frequentes foram diminuição da fração de ejeção do ventrículo esquerdo, infarto do miocárdio, alterações no eletrocardiograma, insuficiência cardíaca e angina, enquanto que os vasculares periféricos foram hipertensão arterial e tromboembolismo.

Conclusão:

A terapia antineoplásica oral está associada a diferentes eventos adversos, dentre eles os cardíacos e os vasculares periféricos.

Descritores:
Antineoplásicos; Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos; Cardiotoxicidade; Sistema Cardiovascular; Revisão

Título	País/Ano	Delineamento/Amostra do estudo	Desfecho
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... ⁾	Estados Unidos/ 2013	Coorte 289 pacientes com carcinoma de célula renal avançado	- Sunitinibe: insuficiência cardíaca (2%), doença arterial coronariana (9%) e fibrilação atrial (1%). - Sorafenibe: insuficiência cardíaca (4%), doença arterial coronariana (5%) e fibrilação atrial (4%). - Pazopanibe: insuficiência cardíaca (2%), doença arterial coronariana (2%) e fibrilação atrial (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... ⁾	Estados Unidos, 2008	Coorte 86 pacientes com carcinoma de célula renal metastático	- Sunitinibe ou sorafenibe: alterações no eletrocardiograma (46,5%), diminuição da fração de ejeção do ventrículo esquerdo (10,4%); derrame pericárdico (1%), elevação de enzimas cardíacas (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... ⁾	Estados Unidos, 2010	Ensaio clínico 33 pacientes de 2 a 21 anos, com tumores sólidos refratários	- Sunitinibe: Redução da fração de ejeção cardíaca (8,6%), prolongamento de QTc no eletrocardiograma (8,6%).
Hyperlipidemia and Hypothyroidism Among Metastatic Renal Cell Carcinoma Patients Taking Sunitinib Malate. Related or Unrelated Adverse Events? ⁽ 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... ⁾	Estados Unidos, 2015	Coorte 39 pacientes com carcinoma de célula renal metastático	- Sunitinibe: Diminuição da função do ventrículo esquerdo e óbito após infarto do miocárdio (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... ⁾	Estados Unidos, 2007	Ensaio clínico 750 pacientes com carcinoma de célula renal metastático	- Sunitinibe: diminuição da fração de ejeção do ventrículo esquerdo (2%). - Interferon alfa: diminuição fração de ejeção do ventrículo esquerdo (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... ⁾	Estados Unidos, 2010	Coorte 219 pacientes com sarcoma	- Imatinibe: Isquemia cardíaca ou dor no peito (2,3%), arritmias (0,9%); alterações no eletrocardiograma (1%), disfunção do ventrículo esquerdo (0,4%), parada cardíaca (0,4%), insuficiência cardíaca (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... ⁾	Estados Unidos, 2010	Ensaio clínico 296 mulheres com câncer de mama HER2 positivo metastático	- Lapatinibe: Diminuição da fração de ejeção do ventrículo esquerdo (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... ⁾	Estados Unidos, 2010	Ensaio clínico 29 pacientes com tumores sólidos avançados	- Dasatinibe: Prolongamento de intervalo QTc no eletrocardiograma (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... ⁾	Estados Unidos, 1989	Ensaio clínico 76 pacientes com câncer de mama avançado	- Idarrubicina: Diminuição da fração de ejeção do ventrículo esquerdo (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... ⁾	Estados Unidos, 1988	Ensaio clínico 15 crianças com leucemia aguda refratária	- Idarrubicina: Diminuição da fração de ejeção do ventrículo esquerdo (6,6%) e diminuição da fração de encurtamento (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... ⁾	Estados Unidos, 2000	Ensaio clínico 109 pacientes com câncer colorretal avançado	- Capecitabina: Angina (1,8%), fibrilação atrial (0,9%) e dor no peito (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... ⁾	Inglaterra, 2008	Coorte 48 pacientes com carcinoma de célula renal ou tumor de estroma gastrointestinal	- Sunitinibe: disfunção ventricular com diminuição da fração de ejeção do ventrículo esquerdo (12,5%) e choque cardiogênico (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... ⁾	Inglaterra, 2007	Coorte 75 pacientes com tumor de estroma gastrointestinal resistente a imatinibe	- Sunitinibe: insuficiência cardíaca congestiva (8%), diminuição da fração de ejeção do ventrículo esquerdo (28%), troponina elevada (18%) e óbito após infarto do miocárdio (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... ⁾	Inglaterra, 2009	Coorte 175 pacientes com carcinoma de célula renal metastático	- Sunitinibe: diminuição da fração de ejeção do ventrículo esquerdo (18,9%) e insuficiência cardíaca congestiva (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... ⁾	Inglaterra, 2015	Metanálise 6548 pacientes com carcinoma hepatocelular, sarcoma de partes moles, carcinoma de célula renal, câncer colorretal, de próstata, pâncreas, mama, tireoide, pulmão ou vesícula biliar	- Inibidores da tirosina quinase em geral: alterações no eletrocardiograma (4,4%, RR= 66, IC= 95% e p=0.001 em relação à outros antineoplásicos). - Axitinibe: taquicardia ventricular (0,33%). - Capecitabina: Fibrilação atrial (0,93%). - Vandetanibe: Fibrilação atrial (0,56%), taquicardia ventricular (1,37%) e parada cardíaca (0,15%). - Pazopanibe: fibrilação atrial (0,37%) e parada cardíaca (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... ⁾	Inglaterra, 2006	Ensaio clínico 6241 mulheres após a menopausa com câncer de mama	- Anastrozole: angina, infarto do miocárdio, isquemia do miocárdio e desordem arterial coronariana (2%). - Tamoxifeno: Angina, isquemia do miocárdio e desordem arterial coronariana (2%) e infarto do miocárdio (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... ⁾	Inglaterra, 1985	Ensaio clínico 29 pacientes com câncer de mama avançado	- Idarrubicina: Alterações no eletrocardiograma (6,8%) e diminuição da fração de ejeção do ventrículo esquerdo (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... ⁾	Alemanha, 2013	Ensaio clínico 95 pacientes com tumores sólidos avançados	- Pazopanibe: diminuição da frequência cardíaca (média= 9,9 bpm), prolongamento de 4.4 ms em segmento QTc (90 % CI: -2.4, 11.2), em comparação ao 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... ⁾	Itália, 2012	Coorte 81 pacientes previamente tratados com nilotinibe	- Nilotinibe: Infarto do miocárdio (2,4%), síndrome coronariana aguda (7,4%), fibrilação atrial (1,2%), angina (1,2%) e alterações em eletrocardiograma (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/... ⁾	Noruega, 2012	Caso-controle 334 pacientes com prolactinoma	- Cabergolina: Derrame pericárdico assintomático (0,9%) e risco de fibrose valvular (OR=2.27, p= 0.016). - Bromocriptina: Derrame pericárdico assintomático (1,8%) e risco de fibrose valvular (OR=2.66, p= 0.014).

Título	Ano/País	Delineamento/Amostra do estudo	Desfecho
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... ⁾	Estados Unidos, 2013	Coorte 289 pacientes com carcinoma de célula renal avançado	- Sunutinibe: hipertensão arterial (44%). - Sorafenibe: hipertensão arterial (52%). - Pazopanibe: hipertensão arterial (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... ⁾	Estados Unidos, 2008	Coorte 86 pacientes com carcinoma de célula renal metastático	- Sunitinibe ou sorafenibe: neuropatia ótica isquêmica e oclusão de artéria tibial posterior (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... ⁾	Estados Unidos, 2010	Ensaio clínico 33 pacientes de 2 a 21 anos, com tumores sólidos refratários	- Sunitinibe: Hipertensão arterial (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... ⁾	Estados Unidos, 2007	Ensaio clínico 750 pacientes com carcinoma de célula renal metastático	- Sunitinibe: hipertensão arterial (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... ⁾	Estados Unidos, 2008	Ensaio clínico 18 pacientes com tumores sólidos	- Telatinibe: Aumento da pressão arterial (78%); enrijecimento arterial (velocidade da onda de pulso aórtico aumentada em 94% dos pacientes, p=0,001), diminuição da densidade capilar e diminuição do fluxo sanguíneo da pele (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... ⁾	Estados Unidos, 2005	Ensaio clínico 41 pacientes com mieloma múltiplo	- Melfalano + Prednisona + talidomida: Eventos tromboembólicos (20%).
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... ⁾	Inglaterra, 2007	Coorte 75 pacientes com tumor de estroma gastrointestinal resistente a imatinibe	- Sunitinibe: hipertensão arterial (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... ⁾	Inglaterra, 2009	Coorte 175 pacientes com carcinoma de célula renal metastático	- Sunitinibe: hipertensão arterial (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... ⁾	Inglaterra, 2006	Ensaio clínico 312 pacientes com tumor de estroma gastrointestinal resistente a imatinibe	- Sunitinibe: Hipertensão arterial (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... ⁾	Inglaterra, 2006	Ensaio clínico 6241 mulheres após a menopausa com câncer de mama	- Anastrozole: eventos venosos tromboembólicos (3%) e hipertensão (13%). - Tamoxifeno: eventos venosos tromboembólicos e hipertensão (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... ⁾	Alemanha, 2013	Ensaio clínico 95 pacientes com tumores sólidos avançados	- Pazopanibe: Aumento transitório da pressão arterial sistólica (média +17.7 mmHg, DP= 14.2) e diastólica (média +11.9 mmHg, DP=6,3) e hipertensão arterial (15%).

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