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1.
Eur Heart J Acute Cardiovasc Care ; 9(3): 215-221, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32372695

RESUMO

More than 2,000,000 individuals worldwide have had coronavirus 2019 disease infection (COVID-19), yet there is no effective medical therapy. Multiple off-label and investigational drugs, such as chloroquine and hydroxychloroquine, have gained broad interest due to positive pre-clinical data and are currently used for treatment of COVID-19. However, some of these medications have potential cardiac adverse effects. This is important because up to one-third of patients with COVID-19 have cardiac injury, which can further increase the risk of cardiomyopathy and arrhythmias. Adverse effects of chloroquine and hydroxychloroquine on cardiac function and conduction are broad and can be fatal. Both drugs have an anti-arrhythmic property and are proarrhythmic. The American Heart Association has listed chloroquine and hydroxychloroquine as agents which can cause direct myocardial toxicity. Similarly, other investigational drugs such as favipiravir and lopinavir/ritonavir can prolong QT interval and cause Torsade de Pointes. Many antibiotics commonly used for the treatment of patients with COVID-19, for instance azithromycin, can also prolong QT interval. This review summarizes evidenced-based data regarding potential cardiac adverse effects due to off-label and investigational drugs including chloroquine and hydroxychloroquine, antiviral therapy, monoclonal antibodies, as well as common antibiotics used for the treatment of COVID-19. The article focuses on practical points and offers a point-of-care protocol for providers who are taking care of patients with COVID-19 in an inpatient and outpatient setting. The proposed protocol is taking into consideration that resources during the pandemic are limited.


Assuntos
Antimaláricos/efeitos adversos , Betacoronavirus/efeitos dos fármacos , Cloroquina/efeitos adversos , Infecções por Coronavirus/tratamento farmacológico , Monitoramento de Medicamentos/métodos , Hidroxicloroquina/efeitos adversos , Pneumonia Viral/tratamento farmacológico , Antibacterianos/efeitos adversos , Anticorpos Monoclonais/efeitos adversos , Antimaláricos/farmacocinética , Antimaláricos/toxicidade , Arritmias Cardíacas/induzido quimicamente , Arritmias Cardíacas/complicações , Cardiomiopatias/induzido quimicamente , Cardiomiopatias/complicações , Cardiotoxicidade/epidemiologia , Cloroquina/farmacocinética , Cloroquina/toxicidade , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Inibidores do Citocromo P-450 CYP3A/efeitos adversos , Humanos , Hidroxicloroquina/farmacocinética , Hidroxicloroquina/toxicidade , Uso Off-Label/estatística & dados numéricos , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Torsades de Pointes/induzido quimicamente , Torsades de Pointes/epidemiologia
2.
Exp Oncol ; 41(4): 353-356, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31868328

RESUMO

AIM: To evaluate the quality of life (QoL) parameters in patients with acute leukemia (AL) during standard induction chemotherapy, depending on the presence of concomitant ischemic heart disease and to improve them by the prevention of anthracycline cardiotoxicity with L-arginine. MATERIALS AND METHODS: A total of 147 adult AL patients (72 males and 75 females with the mean age 54.7 ± 9.3 years) were enrolled in the study. QoL assessment was performed at baseline and after induction chemotherapy using SF-36 questionnaire. Both physical and mental parameters were evaluated. RESULTS: The QoL analysis of patients with AL at the time of initial diagnosis showed extremely low QoL level in all subgroups compared with healthy individuals. It should be noted that the level of patients' QoL after achieving remission remained significantly lower than those of practically healthy, which is primarily due to the need for further long-term treatment and, probably, the fear of the disease relapse development. It was found that the administration of L-arginine during induction chemotherapy in order to reduce the risk of anthracycline cardiotoxicity development has allowed improving the QoL in patients with concomitant ischemic heart disease. CONCLUSION: L-arginine decreases the risk of anthracycline-induced myocardial injury and improves QoL in AL patients.


Assuntos
Antraciclinas/uso terapêutico , Antibióticos Antineoplásicos/uso terapêutico , Arginina/uso terapêutico , Cardiotoxicidade/prevenção & controle , Crioprotetores/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Adulto , Antraciclinas/efeitos adversos , Antibióticos Antineoplásicos/efeitos adversos , Cardiotoxicidade/epidemiologia , Comorbidade , Feminino , Humanos , Quimioterapia de Indução , Leucemia Mieloide Aguda/epidemiologia , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/epidemiologia , Qualidade de Vida
3.
Curr Oncol ; 26(3): e314-e321, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31285674

RESUMO

Background: Clinical trials have demonstrated an increased risk of cardiotoxicity in patients with breast cancer (bca) receiving trastuzumab-based therapy. Diabetes, dyslipidemia, and obesity are known risk factors for cardiovascular disease. Studies have yielded conflicting results about whether those factors increase the risk of cardiotoxicity in patients with bca receiving trastuzumab. Methods: In this retrospective cohort study, data were collected for 243 patients with bca positive for her2 (the human epidermal growth factor receptor 2) who were receiving trastuzumab and who were referred to The Ottawa Hospital Cardio-oncology Referral Clinic between 2008 and 2013. The data collected included patient demographics, reason for referral, cardiac function, chemotherapy regimen (including anthracycline use), and 3 comorbidities (diabetes, dyslipidemia, obesity). Rates of symptomatic cancer treatment-related cardiac dysfunction (sctcd) and asymptomatic decline in left ventricular ejection fraction (adlvef) were calculated for patients with and without the comorbidities of interest. Results: Of the 243 identified patients, 104 had either diabetes, dyslipidemia, or obesity. In that population, the most likely reason for referral to the cardio-oncology clinic was adlvef. The combination of 2 or 3 comorbidities significantly increased the incidence of sctcd in our population, reaching a rate of 67% for patients with obesity and dyslipidemia [relative risk (rr): 2.2; p = 0.04], 69% for patients with obesity and diabetes (rr: 2.3; p = 0.02), and 72% for patients with all 3 risk factors (rr: 2.4; p = 0.08). Conclusions: The combination of 2 or 3 comorbidities significantly increases the incidence of symptomatic cancer treatment-related cardiotoxicity. Patients with bca experiencing cancer treatment-related cardiotoxicity who have a history of diabetes, dyslipidemia, and obesity might require more proactive strategies for prevention, detection, and treatment of cardiotoxicity while receiving trastuzumab-based treatment.


Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Neoplasias da Mama/epidemiologia , Cardiotoxicidade/epidemiologia , Diabetes Mellitus/epidemiologia , Dislipidemias/epidemiologia , Obesidade/epidemiologia , Trastuzumab/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Diabetes Mellitus/tratamento farmacológico , Dislipidemias/tratamento farmacológico , Feminino , Humanos , Pessoa de Meia-Idade , Obesidade/tratamento farmacológico , Estudos Retrospectivos , Fatores de Risco
4.
Crit Rev Oncol Hematol ; 141: 95-101, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31272046

RESUMO

BACKGROUND: Cancer and heart diseases are the leading causes of morbidity and mortality in many countries worldwide. Recent advancement in chemotherapy and targeted therapies has led to an improvement in cancer survival rates, but at a cost of higher cardiac side effects. However, report on antineoplastic-related cardiotoxicities incidence in Asia is lacking. METHODS: We systematically searched multiple databases to identify studies reporting incidence of antineoplastic-related cardiovascular toxicity in Asia published from inception to November 2018. Pre-specified subgroups were performed to explore heterogeneity and study quality assessed and reported according to PRISMA guidelines. RESULTS: A total of 61 studies across 11 countries in Asia reported 8 types of cardiovascular toxicities were included. These studies mostly reported on adult populations, and usually examined cardiotoxicities related to anthracycline use. The most frequently reported cardiotoxicities were heart failure, electrocardiogram abnormalities and left ventricular dysfunction. The pooled estimated incidence of cardiotoxicity was 4.27% (95% CI: 3.53-5.07). Subgroup analysis showed higher incidence in middle income countries compared to high income countries. CONCLUSIONS: Although robust incidence studies are sparse, cardiovascular complications affects approximately one in twenty cancer patients in Asia. This highlights a unique opportunity of cancer patients caring that need cardiologists and oncologist to become familiar with this emerging sub-specialty.


Assuntos
Antraciclinas/efeitos adversos , Antibióticos Antineoplásicos/efeitos adversos , Cardiopatias/induzido quimicamente , Neoplasias/tratamento farmacológico , Adulto , Antraciclinas/classificação , Antraciclinas/uso terapêutico , Antibióticos Antineoplásicos/classificação , Antibióticos Antineoplásicos/uso terapêutico , Ásia/epidemiologia , Cardiotoxicidade/epidemiologia , Cardiopatias/epidemiologia , Humanos , Incidência , Neoplasias/epidemiologia
5.
Heart Fail Rev ; 24(6): 915-925, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31256318

RESUMO

Anthracyclines are the cornerstone for many oncologic treatments, but their cardiotoxicity has been recognized for several decades. Female subjects, especially before puberty and adolescence, or after menopause, seem to be more at increased risk, with the prognostic impact of this sex issue being less consistent compared to other cardiovascular risk factors. Several studies imply that sex differences could depend on the lack of the protective effect of sex hormones against the anthracycline-initiated damage in cardiac cells, or on differential mitochondria-related oxidative gene expression. This is also reflected by the results obtained with different diagnostic methods, such as cardiovascular biomarkers and imaging techniques (echocardiography, magnetic resonance, and nuclear medicine) in the diagnosis and monitoring of cardiotoxicity, confirming that sex differences exist. The same is true about protective strategies from anthracycline cardiotoxicity. Indeed, first studied to withstand oxidative damage in response to ischemia/reperfusion (I/R) injury, cardioprotection has different outcomes in men and women. A number of studies assessed the differences in I/R response between male and female hearts, with oxidative stress and apoptosis being shared mechanisms between the I/R and anthracyclines heart damage. Sex hormones can modulate these mechanisms, thus confirming their importance in the pathophysiology in cardioprotection not only from the ischemia/reperfusion damage, but also from anthracyclines, fueling further cardio-oncologic research on the topic.


Assuntos
Antraciclinas/toxicidade , Cardiotoxicidade/etiologia , Insuficiência Cardíaca/induzido quimicamente , Coração/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Antraciclinas/efeitos adversos , Biomarcadores/metabolismo , Cardiotônicos/farmacologia , Cardiotoxicidade/diagnóstico por imagem , Cardiotoxicidade/epidemiologia , Cardiotoxicidade/metabolismo , Ecocardiografia/métodos , Feminino , Hormônios Esteroides Gonadais/farmacologia , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Espectroscopia de Ressonância Magnética/métodos , Masculino , Mitocôndrias/metabolismo , Medicina Nuclear/métodos , Estresse Oxidativo/efeitos dos fármacos , Prognóstico , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/prevenção & controle , Fatores de Risco , Caracteres Sexuais
6.
Afr Health Sci ; 19(1): 1647-1656, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31148994

RESUMO

Purpose: To determine the cumulative incidence of anthracycline induced cardiotoxicity (AIC), its predictors, and associated electrocardiographic and echocardiographic manifestations in adult cancer patients at Uganda Cancer Institute (UCI). Methods: We enrolled 160 participants between June 2013 and April 2014 and followed them up for a median of 146 days. Data on clinical, electrocardiographic and echocardiographic findings was obtained at baseline, and at completion of chemotherapy. The Pearson chi square test was used to identify the predictors associated with cardiotoxicity. Results: Of the 64 patients who were accessible for follow-up electrocardiography (ECG) and echocardiography (ECHO), fourteen participants developed cardiotoxicity hence a cumulative incidence rate of 21.9% with 95% CI 13.5%-33.43%. The predictors of AIC were female gender (p=0.025), LVEF (p=0.014) and LVFS (P=0.019). Anthracycline therapy was associated with shortening of the QRS duration (84.3±7.9 Vs 82.1±11.8 ms, p=0.005), prolongation of the QTc interval (411.9±30.7 Vs 447.2±39.4 ms, p=<0.001) and reduction in the LVEF (66.4±7.7 Vs 63.9±8.4%, p=0.026) and LVFS (36.9±6.2 Vs 35.1±6.6%, p=0.03). Conclusion: The cumulative incidence of AIC in this study cohort was high. Our findings emphasize the need for early monitoring for AIC.


Assuntos
Antraciclinas/efeitos adversos , Antineoplásicos/efeitos adversos , Arritmias Cardíacas/diagnóstico , Cardiotoxicidade/diagnóstico , Ecocardiografia/métodos , Eletrocardiografia/métodos , Coração/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Arritmias Cardíacas/induzido quimicamente , Cardiotoxicidade/epidemiologia , Estudos de Coortes , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Neoplasias/epidemiologia , Estudos Prospectivos , Uganda/epidemiologia
7.
Breast Cancer Res Treat ; 177(2): 237-250, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31165940

RESUMO

BACKGROUND: Breast cancer is a leading cause of death for women worldwide, with incidence increasing in lower-income countries. For patients with human epidermal growth factor receptor-2-positive (HER2+) breast cancer, widespread availability of several agents targeting the HER2 receptor has resulted in survival gains over the past decades. However, improved survival has resulted in an increased need for management and mitigation of adverse events associated with anticancer therapy. Cardiac adverse events such as decreased ejection fraction and heart failure have been of particular concern in patients with HER2+ breast cancer. Anti-HER2 agents and chemotherapies (specifically anthracyclines, which are frequently used to treat HER2+ disease) have been associated with cardiotoxicity. As increasing numbers of patients are living longer due to more effective therapy, a better understanding of both monitoring and management of cardiotoxicity is urgently needed. METHODS: A comprehensive review of the literature was conducted via PubMed in January 2018 for phase II and phase III trials of "trastuzumab", "lapatinib", "pertuzumab", "T-DM1", "neratinib", in "breast cancer". Literature was evaluated for content related to cardiac adverse events. FINDINGS: We describe the incidence of and proposed mechanisms for the cardiotoxicity of available HER2-targeted therapies. We summarize current and emerging practices in the management of cardiotoxicity and provide guidance for routine patient care in real-world practice using illustrative patient scenarios. CONCLUSIONS: The future of cardiotoxicity management in patients with HER2+ breast cancer is discussed, with a focus on novel techniques to improve cardiac outcomes, including new imaging modalities, biomarkers, interventional therapies, and ongoing trials.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/complicações , Neoplasias da Mama/genética , Cardiotoxicidade/etiologia , Variantes Farmacogenômicos , Receptor ErbB-2/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Cardiotoxicidade/diagnóstico , Cardiotoxicidade/epidemiologia , Ensaios Clínicos como Assunto , Gerenciamento Clínico , Monitoramento de Medicamentos , Feminino , Humanos , Incidência , Terapia de Alvo Molecular/efeitos adversos , Terapia de Alvo Molecular/métodos , Receptor ErbB-2/antagonistas & inibidores
8.
Cancer Chemother Pharmacol ; 84(3): 599-607, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31203389

RESUMO

OBJECTIVES: Cardiotoxicity is an important side effect in patients receiving chemotherapy and the application of anthracycline drugs for gastric cancer treatment is uncommon. The purpose of this study was to determine the incidence rate of and risk factors for cardiotoxicity in gastric cancer patients treated with fluorouracil-based chemotherapy. MATERIALS AND METHODS: We retrospectively enrolled patients with locally advanced or metastatic gastric cancer from 2011 to 2016. Patients were treated with multiple cycles of fluorouracil-based chemotherapy at Peking University First Hospital. The incidence of cardiotoxicity and patients' clinical data were obtained from hospital clinical databases and manually reviewed. RESULTS: A total of 129 patients were eligible for and were enrolled in this study. A median of 6 chemotherapy cycles were administered (range 1-18 cycles). Cardiotoxicity was observed in 38 of 129 patients (29.5%). Twelve patients (9.3%) exhibited toxicity greater than grade 2, and 2 (1.6%) patients died of cardiac toxicity. The only independent risk factor for serious cardiotoxicity identified by multivariable analysis was a history of cardiac disease (OR 4.108, 95% CI 2.778-6.074, P < 0.001). CONCLUSIONS: Chemotherapy-related cardiotoxicity may be underestimated in Chinese gastric cancer patients. Close monitoring for cardiotoxicity and enhanced cardiac management are recommended for patients who receive fluorouracil-based chemotherapy, especially for patients with high-risk factors for serious cardiotoxicity. New strategies, such as identifying the administration schedule of fluorouracil with minimal cardiotoxicity, and cardio-oncology, are necessary to prevent and treat chemotherapy-induced cardiotoxicity.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cardiotoxicidade/epidemiologia , Cardiotoxicidade/etiologia , Neoplasias Gástricas/tratamento farmacológico , Adenocarcinoma/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Capecitabina/administração & dosagem , Cardiotoxicidade/patologia , Cisplatino/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Seguimentos , Humanos , Incidência , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Oxaliplatina/administração & dosagem , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Neoplasias Gástricas/patologia , Taxa de Sobrevida
9.
Heart Fail Rev ; 24(6): 989-995, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31175492

RESUMO

Cancer is the second leading cause of death in the USA, and cardiovascular disease is the second leading cause of morbidity and mortality among cancer survivors. Cancer survivors share common risk factors for cardiovascular disease with non-cancer patients. With improved survival, cancer patients become susceptible to treatment-related toxicity often involving the heart. The impact of concurrent malignancy on outcomes particularly among heart failure patients is an area of active research. We studied the trends in the prevalence of a concurrent diagnosis of breast, prostate, colorectal, and lung cancer among admissions for acute heart failure and the associated trends for in-hospital mortality. Patients aged ≥ 18 years who were admitted with a primary diagnosis of "congestive heart failure" (CCS codes 99 and 108) from years 2003 to 2014 were included. We analyzed the rate of admission and in-hospital mortality among patients who had a concurrent diagnosis for either lung cancer, colorectal cancer, breast cancer (among females), or prostate cancer (among males). We performed a multivariate analysis to assess the role of a concurrent diagnosis of any cancer in predicting in-hospital mortality among HF admissions. From 2003 to 2014 across over 12 million HF admissions, ≈ 7% had a concurrent diagnosis of either lung, breast, colorectal, or prostate cancer. The prevalence was highest for breast cancer (2.3%) followed by prostate cancer (2.1%) and colorectal cancer (1.5%) and lowest with lung cancer (1.1%). The prevalence of cancer increased over the duration of study among all four cancer types with the largest increase in prevalence of breast cancer. Baseline comorbidities including hypertension, diabetes, smoking, chronic kidney disease, and coronary artery disease increased over time among patients with and without cancer. In-hospital mortality was higher among those with a diagnosis of lung cancer (5.9%) followed by colorectal cancer (4.0%), prostate cancer (3.5%), no diagnosis of cancer (3.3%), and breast cancer (3.2%). In-hospital mortality declined across HF admissions with and without a cancer diagnosis from 2003 to 2014. Decline in such mortality among heart failure was highest for patients with lung cancer (8.1 to 4.6% from 2003 to 2014; p < 0.001). Multivariate analysis showed that a concurrent diagnosis of cancer was associated with a marginally lower hospital mortality compared with controls (adjusted odds ratio 0.95, 95% confidence interval 0.94-0.96; p < 0.001). Among HF admissions, the prevalence of a concurrent cancer diagnosis increased over time for breast, lung, colorectal, and prostate cancer. Baseline in-hospital mortality was higher among HF admissions with either lung cancer, colorectal cancer, or prostate cancer and lower with breast cancer compared with controls without a cancer diagnosis. Adjusted analysis revealed no evidence for higher hospital mortality among HF admissions with any accompanying cancer diagnosis.


Assuntos
Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/mortalidade , Mortalidade Hospitalar/tendências , Hospitalização/tendências , Neoplasias/epidemiologia , Neoplasias/mortalidade , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/epidemiologia , Sobreviventes de Câncer/estatística & dados numéricos , Cardiotoxicidade/complicações , Cardiotoxicidade/epidemiologia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Comorbidade , Feminino , Insuficiência Cardíaca/diagnóstico , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/epidemiologia , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Prevalência , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/epidemiologia , Fatores de Risco
10.
Oncol Res Treat ; 42(7-8): 405-413, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31104059

RESUMO

The effects of anthracycline-based chemical therapies on breast cancer are controversial and inconclusive. We undertook a network meta-analysis to assess the cardiotoxicity and effects of anthracycline therapies in breast cancer. The PubMed, Embase, and Cochrane databases up to August 2018 were reviewed. We identified 19 randomized clinical trials including 3,484 patients with breast cancer which assessed both cardiotoxicity and the effects of anthracycline-based therapies. Eligible studies included the following five treatment strategies: doxorubicin, epirubicin, liposomal doxorubicin (LD), doxorubicin + dexrazoxane (DD), and epirubicin + dexrazoxane (ED). In a direct meta-analysis, epirubicin, LD, DD, and ED had significantly superior cardioprotective effects compared with doxorubicin with odds ratios and 95% CIs of 1.64 (1.04, 2.57), 3.75 (2.46, 5.70), 2.88 (1.93, 4.29), and 3.66 (1.09, 12.33), respectively. Doxorubicin showed no significant difference of response rate compared with epirubicin or LD or DD, respectively. In a network meta-analysis, the ranking order of cardiotoxicity was doxorubicin (worst), epirubicin, DD, LD, and ED (best). The ranking order of the response rate was LD (best), doxorubicin, epirubicin, ED, and DD (worst). The most favorable balance between benefit and risk was shown for ED (best) followed by LD, DD, epirubicin, and doxorubicin. In conclusion, LD or ED is the suitable anthracycline treatment for breast cancer in consideration of both cardiotoxicity and efficacy.


Assuntos
Antraciclinas/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Cardiotoxicidade/epidemiologia , Antraciclinas/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Humanos , Metanálise em Rede , Resultado do Tratamento
11.
Drug Deliv ; 26(1): 433-442, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30929538

RESUMO

Doxorubicin (DOX) is one of the most widely used anticancer agents. DOX is known for inducing cardiotoxicity, resulting in the long-term development of heart failure. Intravascular delivery of DOX may benefit from the carriage by red blood cells (RBCs), as they can limit the systemic toxicity while delivering the DOX to the tumor. This study proposes a methodology for the synthesis of electrophoretically DOX-loaded red blood cells (RBC-DOX), as well as the assessment of its antitumorigenic effects in human colon cancer cells (HT-29), and in colon cancer xenograft models. In addition, healthy mice without tumors were dosed with RBC-DOX to assess cardiotoxicity via assessment of indexes of cardiac function after multiple doses of RBC-DOX. The HT-29 IC50 was found to be lower for RBC-DOX compared to free DOX. Tumor volume for the RBC-DOX group was smaller than the free DOX groups in HT-29 xenografts models. Statistically higher concentrations of DOX were found in the liver, spleen, and lungs for the RBC-DOX group compared to the free DOX group. However, the heart and the skin had statistically lower DOX concentrations for the RBC-DOX group compared to the free DOX group, with no significant differences in tumor biodistribution. All hemodynamic and cardiac function parameters were closer to control parameters for the RBC-DOX treated compared to for the free DOX-treated mice. These results suggest that RBC-DOX can be an alternative to prolong treatments with DOX, with superior antitumorigenic effects, decreased myelosuppression, and limited cardiac toxicity compared to equivalent doses of free DOX.


Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Cardiotoxicidade/etiologia , Neoplasias do Colo/tratamento farmacológico , Doxorrubicina/administração & dosagem , Eritrócitos/metabolismo , Animais , Antibióticos Antineoplásicos/farmacologia , Antibióticos Antineoplásicos/toxicidade , Cardiotoxicidade/epidemiologia , Doxorrubicina/farmacologia , Doxorrubicina/toxicidade , Eletroforese , Feminino , Células HT29 , Humanos , Concentração Inibidora 50 , Fígado/metabolismo , Pulmão/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Baço/metabolismo , Distribuição Tecidual , Ensaios Antitumorais Modelo de Xenoenxerto
12.
Breast J ; 25(3): 444-449, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30932296

RESUMO

BACKGROUND: Significant and symptomatic cardiac comorbidity is a contraindication to adjuvant trastuzumab in breast cancer patients. However, some patients with asymptomatic, nonlimiting cardiac comorbidity and normal baseline left ventricular ejection fraction (LVEF) receive adjuvant trastuzumab in the clinical practice. We sought to describe the tolerability of trastuzumab in these patients. PATIENTS AND METHODS: Retrospective analysis of patients with baseline asymptomatic, nonlimiting cardiac comorbidity receiving adjuvant trastuzumab at six Institutions between July 2007 and January 2016. RESULTS: Thirty-seven patients with HER2-positive, surgery treated breast cancer at high risk of relapse were studied. Median age was 64 years (range 36-82), median baseline LVEF 61% (range 50%-85%). Thirteen patients (35%) received trastuzumab with adjuvant anthracycline and taxane-based regimens, 19 (51%) with taxane-based, three (8%) with off-label vinorelbine and two (5%) with off-label endocrine therapy. Most frequent cardiac comorbidities were ischemic heart disease (35%), valvular disease (30%), atrial fibrillation (19%), and conduction disorders (14%). Nine patients (24.3%) experienced a cardiac event: congestive heart failure (one patient, 3%), asymptomatic LVEF reduction (six patients, 16%), and rhythm disturbances (two patients, 5%). Trastuzumab had to be discontinued either permanently (five patients, 14%) or temporarily (two patients, 5%). At the time of last follow-up visit, all patients showed LVEF within normal limits, except one who had experienced a symptomatic cardiac event (LVEF value at last follow-up 46%). CONCLUSIONS: Caution is needed in patients with significant ongoing cardiovascular risk factors, but when adjuvant trastuzumab is deemed beneficial on breast cancer outcomes, nonlimiting cardiac comorbidity should not preclude treatment.


Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Cardiotoxicidade/etiologia , Trastuzumab/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/epidemiologia , Cardiotoxicidade/epidemiologia , Feminino , Cardiopatias/epidemiologia , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Trastuzumab/administração & dosagem , Resultado do Tratamento , Disfunção Ventricular Esquerda/epidemiologia , Disfunção Ventricular Esquerda/etiologia
13.
JAMA Oncol ; 5(6): 864-871, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30703192

RESUMO

Importance: Anthracyclines are part of many effective pediatric cancer treatment protocols. Most pediatric oncology treatment groups assume that the hematologic toxicity of anthracycline agents is equivalent to their cardiotoxicity; for example, Children's Oncology Group substitution rules consider daunorubicin and epirubicin isoequivalent to doxorubicin, whereas mitoxantrone and idarubicin are considered 4 to 5 times as toxic as doxorubicin. Objective: To determine optimal dose equivalence ratios for late-onset cardiomyopathy between doxorubicin and other anthracyclines or the anthraquinone mitoxantrone. Design, Setting, and Participants: This multicenter cohort study of childhood cancer survivors who survived 5 or more years analyzed data pooled from 20 367 participants in the Childhood Cancer Survivor Study treated from 1970 to 1999, 5741 participants in the Dutch Childhood Oncology Group LATER study diagnosed between 1963 and 2001, and 2315 participants in the St Jude Lifetime study treated from 1962 to 2005. Exposures: Cumulative doses of each agent (the anthracyclines doxorubicin, daunorubicin, epirubicin, and idarubicin; and the anthraquinone mitoxantrone) along with chest radiotherapy exposure were abstracted from medical records. Main Outcomes and Measures: Cardiomyopathy (severe, life-threatening, or fatal) by 40 years of age. Agent-specific Cox proportional hazards models evaluated cardiomyopathy risk, adjusting for chest radiotherapy, age at cancer diagnosis, sex, and exposure to anthracyclines or to an anthraquinone. An agent-specific cardiomyopathy equivalence ratio (relative to doxorubicin) was estimated for each dose category as a ratio of the hazard ratios, and then a weighted mean determined the overall agent-specific equivalence ratio across all dose categories. Results: Of 28 423 survivors (46.4% female; median age at cancer diagnosis 6.1 years [range, 0.0-22.7 years]), 9330 patients received doxorubicin, 4433 received daunorubicin, 342 received epirubicin, 241 received idarubicin, and 265 received mitoxantrone. After a median follow-up of 20.0 years (range, 5.0-40.0 years) following receipt of a cancer diagnosis, 399 cardiomyopathy cases were observed. Relative to doxorubicin, the equivalence ratios were 0.6 (95% CI, 0.4-1.0) for daunorubicin, 0.8 (95% CI, 0.5-2.8) for epirubicin, and 10.5 (95% CI, 6.2-19.1) for mitoxantrone. Outcomes were too rare to generate idarubicin-specific estimates. Ratios based on a continuous linear dose-response relationship were similar for daunorubicin (0.5 [95% CI, 0.4-0.7]) and epirubicin (0.8 [95% CI, 0.3-1.4]). The relationship between mitoxantrone and doxorubicin appeared better characterized by a linear exponential model. Conclusions and Relevance: In a large data set assembled to examine long-term cardiomyopathy risk in childhood cancer survivors, daunorubicin was associated with decreased cardiomyopathy risk vs doxorubicin, whereas epirubicin was approximately isoequivalent. By contrast, the current hematologic-based doxorubicin dose equivalency of mitoxantrone (4:1) appeared to significantly underestimate the association of mitoxantrone with long-term cardiomyopathy risk.


Assuntos
Antraciclinas/efeitos adversos , Antibióticos Antineoplásicos/efeitos adversos , Sobreviventes de Câncer/estatística & dados numéricos , Cardiotoxicidade/epidemiologia , Mitoxantrona/efeitos adversos , Adolescente , Adulto , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Risco , Adulto Jovem
14.
Clin Res Cardiol ; 108(9): 1000-1008, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30778669

RESUMO

AIMS: Acute lymphoblastic leukemia (ALL) is one of the leading malignancies in children worldwide. The cardiotoxicity of anti-cancer treatments leads to a dysfunction of the cardiac autonomic nervous system. Protection strategies, with dexrazoxane treatments, were used to counter these adverse effects. The aim of this study was to investigate the effects of the treatments on the cardiac autonomic nervous system. METHODS AND RESULTS: A total of 203 cALL survivors were included in our analyses and were classified into 3 categories based on the prognostic risk group: standard risk, high risk with and without dexrazoxane. A 24-h Holter monitoring was performed to study the cardiac autonomic nervous system. The frequency domain heart rate variability (HRV) was used to validate the cardiac autonomic nervous system modifications. Other analyses were performed using linear HRV indexes in the time domain and non-linear indexes. A frequency domain HRV parameters analysis revealed significant differences on an overall time-period of 24 h. A repeated measures ANOVA indicated a group-effect for the low frequency (p = 0.029), high frequency (p = 0.03) and LF/HF ratio (p = 0.029). Significant differences in the time domain and in the non-linear power spectral density HRV parameters were also observed. CONCLUSION: Anti-cancer treatments induced significant changes in the cardiac autonomic nervous system. The HRV was sensitive enough to detect cardiac autonomic nervous system alterations depending on the cALL risk category. Protection strategies (i.e., dexrazoxane treatments), which were used to counter the adverse effects of doxorubicin, could prevent changes observed in the cardiac autonomic nervous system.


Assuntos
Antibióticos Antineoplásicos/efeitos adversos , Sistema Nervoso Autônomo/efeitos dos fármacos , Cardiotoxicidade/etiologia , Doxorrubicina/efeitos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adolescente , Adulto , Antibióticos Antineoplásicos/administração & dosagem , Sistema Nervoso Autônomo/fisiopatologia , Pressão Sanguínea/fisiologia , Sobreviventes de Câncer , Cardiotoxicidade/epidemiologia , Doxorrubicina/administração & dosagem , Eletrocardiografia Ambulatorial , Frequência Cardíaca/efeitos dos fármacos , Humanos , Prognóstico , Fatores de Risco , Adulto Jovem
15.
BMC Med ; 17(1): 8, 2019 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-30621698
16.
Int J Cardiol ; 280: 163-175, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30661849

RESUMO

Current therapy of advanced cancers is based on several modalities including radiotherapy, cytotoxic chemotherapy, molecularly targeted inhibitors and antibodies targeting immune checkpoints. All of those these modalities can negatively impact the cardiovascular system, and there is considerable experience in relation to radiotherapy and chemotherapy. In contrast, the knowledge base on cardiovascular toxicities of novel agents targeting signal transduction pathways and immune regulation is quite limited. In particular, potential late effects are of concern as cardiovascular pathology can negatively impact quality of life and prognosis in cancer survivors, particularly when additional cardiovascular risk factors are present. Treatment-associated adverse events include hypertension, venous thromboembolism, coronary artery disease, valvular heart disease, heart failure and arrhythmias. Early diagnosis of subclinical cardiotoxic effects of cancer therapies remains challenging. Integrated care, as provided by multidisciplinary cardio-oncology teams is the best option for prevention, diagnosis and treatment of cardiovascular diseases associated with cancer therapy. This review considers the cardiotoxic effects of specific cancer therapies and discusses novel diagnostic and therapeutic approaches as a reference for optimizing the care of cancer patients receiving novel cancer therapies.


Assuntos
Antineoplásicos/efeitos adversos , Cardiologia/métodos , Cardiotoxicidade/prevenção & controle , Doenças Cardiovasculares/terapia , Oncologia/métodos , Radioterapia/efeitos adversos , Cardiotoxicidade/epidemiologia , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/epidemiologia , Gerenciamento Clínico , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/epidemiologia , Neoplasias/radioterapia
17.
Eur J Med Res ; 24(1): 1, 2019 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-30606260

RESUMO

Cancer and cardiovascular diseases are the main causes for morbidity and mortality in modern society. In the United States of America (USA), over 1.7 million new cancer cases will presumably be observed in 2018. Progress in cancer treatment has greatly improved survival and it is estimated that 15.5 million cancer survivors currently live in the USA. The number of cancer survivors is expected to increase by 68% until 2040. Moreover, the portion of cancer survivors at the age of 65 years or older will increase from 62% to approximately 73% in 2040 which in turn enhances comorbidities in cancer survivors. Increased survival and age of cancer patients has unmasked the burden of cancer and cancer therapy-associated cardiovascular diseases. Depending on cancer treatment modalities, early cardiovascular toxicity is observed in up to 48% of patients. Late cardiotoxicity can be found in 30% of patients at 13 years after cancer treatment. Cardio-oncology aims to identify cancer therapy-related cardiovascular side effects and to provide optimum multidisciplinary care for cancer patients. So far, scientific effort has generated a profound knowledge on underlying pathomechanisms and clinical implications but standardized recommendations and structural requirements for cardio-oncology care are still limited.


Assuntos
Sobreviventes de Câncer , Cardiotoxicidade/epidemiologia , Oncologia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Comorbidade , Humanos , Neoplasias/complicações , Neoplasias/terapia
18.
Cancer Chemother Pharmacol ; 83(4): 717-726, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30680521

RESUMO

PURPOSE: Anticancer drugs may cause cardiovascular toxicities, including QT interval prolongation. Niraparib, a potent and selective once-daily oral poly (ADP-ribose) polymerase inhibitor, is approved as a maintenance therapy in platinum-sensitive recurrent epithelial ovarian, fallopian tube, and primary peritoneal cancer (EOC). Here, we present the effects of niraparib on cardiac repolarization, and the correlation between changes in baseline QT interval corrected by Fridericia's formula (ΔQTcF) and niraparib plasma concentrations. METHODS: Patients with EOC from the NOVA study (subset of n = 15), the food effect NOVA substudy (n = 17), and a QTc substudy (n = 26) underwent intensive electrocardiographic (ECG) monitoring that included triplicate ECG testing on Day 1 at baseline (predose) and at 1, 1.5, 2, 3, 4, 6, and 8 h postdose concurrent with time-matched blood sampling for determination of niraparib plasma concentrations. All patients received once-daily 300-mg niraparib until disease progression or toxicity. RESULTS: Across the 3 substudies, the upper limit of the two-sided 90% confidence interval (CI) of ΔQTcF was ≤ 10 ms at every postdose timepoint, with a maximum upper limit of 4.3 ms, which indicates no clinically meaningful effect on QTc prolongation. No statistically significant relationship between ΔQTcF and niraparib plasma concentration was observed (estimated slope: 0.0049; 95% CI: - 0.0020, 0.0117; P = 0.164). There were no clinically relevant changes in other ECG parameters that could be attributable to niraparib. CONCLUSION: Niraparib administration at the recommended daily dose of 300 mg for EOC is not associated with clinically relevant alteration of ECGs, including QTc prolongation.


Assuntos
Cardiotoxicidade/etiologia , Indazóis/efeitos adversos , Síndrome do QT Longo/induzido quimicamente , Piperidinas/efeitos adversos , Inibidores de Poli(ADP-Ribose) Polimerases/efeitos adversos , Idoso , Carcinoma Epitelial do Ovário/tratamento farmacológico , Cardiotoxicidade/epidemiologia , Método Duplo-Cego , Eletrocardiografia , Neoplasias das Tubas Uterinas/tratamento farmacológico , Feminino , Humanos , Indazóis/administração & dosagem , Síndrome do QT Longo/epidemiologia , Pessoa de Meia-Idade , Neoplasias Peritoneais/tratamento farmacológico , Piperidinas/administração & dosagem , Inibidores de Poli(ADP-Ribose) Polimerases/administração & dosagem
20.
Breast Cancer Res Treat ; 174(1): 179-185, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30478787

RESUMO

PURPOSE: Patients with Her2-positive breast cancer treated with trastuzumab have higher rates of cardiotoxicity (CT). Left-breast radiation might increase the risk for CT from cardiac exposure to radiation. The goal of our study is to evaluate the contribution of radiotherapy (RT) in the development of CT in breast cancer patients receiving trastuzumab. METHODS: Two hundred and two patients were treated with RT and trastuzumab from 2000 to 2014. The RT plans for left-side disease were recalled from archives. The heart, each chamber, and left anterior descending artery (LAD) were independently contoured. New dose-volume histograms (DVH) were generated. Their serial left-ventricular ejection fractions (LVEF) were studied. CT for left and right side were compared using Fisher's exact test. The DVH data were correlated with the predefined cardiac events using actuarial Cox regression analysis. RESULTS: Compared to the right sided, the left-side cases showed statistically significant development of arrhythmia (14.2%) versus (< 1%) (p < 0.001). Cardiac ischemia was found in 10 patients in left and one patient in right side (p = 0.011). The equivalent uniform dose (EUD) to the left ventricle (LV), right ventricle (RV), and LAD was significantly associated with decrease in LVEF by > 10% (p = 0.037, p = 0.023 and p = 0.049, respectively). CONCLUSIONS: Among patients treated for left-sided lesions, there were no significant differences in EF decline. However, there was a higher rate of ischemia and arrhythmia compared to those with right-sided disease. The EUD index of LV, RV, and LAD could be considered as a parameter to describe the risk of radiation-induced CT.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/radioterapia , Cardiotoxicidade/etiologia , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Adulto , Idoso , Antineoplásicos Imunológicos/efeitos adversos , Cardiotoxicidade/epidemiologia , Feminino , Humanos , Pessoa de Meia-Idade , Órgãos em Risco , Radioterapia/efeitos adversos , Trastuzumab/efeitos adversos
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