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1.
Zhonghua Yi Xue Za Zhi ; 100(29): 2283-2287, 2020 Aug 04.
Artigo em Chinês | MEDLINE | ID: mdl-32746599

RESUMO

Objective: To explore the role of drug-related molecular target identification in the individualized treatment of malignant solid tumors in children. Methods: The clinical data of 40 patients diagnosed with malignant solid tumors from Beijing Tongren Hospital, Capital Medical University, between June 2017 and March 2019 were retrospectively analyzed. Immunohistochemistry, polymerase chain reaction and sequencing methods were used to determine the expression levels and mutations of tumor drug molecular targets, and to compare the efficiency as well as the incidence of toxic side effects of chemotherapy using anti-tumor drugs with various molecular targets. Results: A total of 4 tumor drug-related targets were identified in 40 tumor tissue samples, namely DNA topoisomerase-ⅡA (TOPOⅡA), ß(3)-tubulin (Tubulinß(3)), DNA topoisomerase-Ⅰ(TOPOⅠ) and dihydrofolate reductase gene polymorphisms [DHFR (C829T)]. The effective rates of platinum-based agents, methotrexate, irinotecan, vinblastine and anthracycline for malignant solid tumors in children were 90.0% (36/40), 85.0% (34/40), 70.0% (28/40), 67.5% (27/40), 62.5% (25/40), respectively. The effective rates of chemotherapy with irinotecan, methotrexate, and vinblastine in mesenchymal tumors were 68.9% (20/29), 62.1% (18/29), 68.9% (20/29), respectively, which were considerably higher than 18.2% (2/11), 36.4% (4/11) and 36.4% (4/11) in non-mesenchymal tumors, with significant differences (χ(2)=5.487, 15.345, 17.278, all P<0.05). The effective rate of chemotherapy of platinum-based drugs for non-mesenchymal tumors was 72.3% (8/11), which was significantly higher than 58.6% (17/29) in mesenchymal tumors, and the difference was statistically significant (χ(2)=11.231, P<0.05). The intensity of toxic side effects in order from high to low was anthracycline > platinum > methotrexate > vinblastine > irinotecan. Conclusion: Tumor drug-related molecular targets and the sensitivity of tumors of different origins to the same anti-tumor drug as well as side effects are predicted, which provides a theoretical and clinical basis for individualized treatment of malignant tumors in children.


Assuntos
DNA Topoisomerases Tipo II , Neoplasias , Antraciclinas , Protocolos de Quimioterapia Combinada Antineoplásica , Criança , Humanos , Estudos Retrospectivos
2.
Adv Exp Med Biol ; 1257: 181-192, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32483740

RESUMO

Doxorubicin is an anthracycline and one of the more effective chemotherapy agents used in the treatment of children, adolescents, and adults with osteosarcoma. Despite its effectiveness, cardiotoxicity is a major late effect that compromises the survival and quality of life of survivors of this and other cancers. Cardiotoxicity is the inability of the heart to pump blood through the body effectively. Doxorubicin-induced cardiotoxicity is dose dependent. Additionally, the age of the patients plays a role in susceptibility with younger patients having a greater risk for cardiotoxicity and heart failure years after treatment is complete. The exact mechanism(s) responsible for doxorubicin-induced cardiotoxicity is poorly understood, and further research needs to be done to elucidate the mechanisms. This chapter summarizes the identified mechanisms that may play a role in anthracycline-induced cardiotoxicity. We will also summarize the types of cardiomyopathies that have been described in survivors treated with doxorubicin and the current recommendations for monitoring survivor for the development of cardiomyopathies. Included will be the important search for defining early biomarkers to identify patients and survivors at risk. Finally, we will summarize some of the interventions proposed for decreasing anthracycline-induced cardiotoxicity.


Assuntos
Antraciclinas , Cardiotoxicidade , Osteossarcoma , Antraciclinas/efeitos adversos , Antibióticos Antineoplásicos/efeitos adversos , Cardiotoxicidade/etiologia , Cardiotoxicidade/prevenção & controle , Humanos , Neoplasias/tratamento farmacológico , Osteossarcoma/tratamento farmacológico , Qualidade de Vida
3.
Medicine (Baltimore) ; 99(25): e20454, 2020 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-32569168

RESUMO

BACKGROUND: The aim of this study is to examine the efficacy of weekly amrubicin (WA) for treating refractory or relapsed non-small cell lung cancer (RRNSCLC). METHODS: The literature search will be performed using the Cochrane Library, MEDLINE, EMBASE, CINAHL, PsycINFO, Scopus, Chinese Biomedical Literature Database, WANGFANG, VIP database, and China National Knowledge Infrastructure from inception onwards up to the March 1, 2020. No language limitation will be implemented. Randomized controlled trials that examined the efficacy and safety of WA for the treatment of RRNSCLC will be included. Literature selection, data extraction, and methodological quality assessment will be handled by 2 independent authors. We will invite a third author to disentangle any divergences between 2 authors. We will carry out statistical analysis using RevMan 5.3 software. RESULTS: This study will summarize current evidence to assess the efficacy and safety of WA for the treatment of RRNSCLC. CONCLUSIONS: The findings of this study will provide helpful evidence for the clinician, and will promote further studies, as well as clarify the direction of research on WA for the management of RRNSCLC.Study registration number: INPLASY202040168.


Assuntos
Antraciclinas/uso terapêutico , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Humanos , Metanálise como Assunto , Revisões Sistemáticas como Assunto
4.
Hinyokika Kiyo ; 66(4): 121-125, 2020 Apr.
Artigo em Japonês | MEDLINE | ID: mdl-32483946

RESUMO

A 68-year-old man was diagnosed with prostate cancer (initial serum prostate specific antigen [PSA] 389 ng/ml, stage cT4N1M1c, Gleason score 5+4), and androgen deprivation therapy was initiated. Despite the low serum PSA level, he developed postrenal acute kidney failure 4 years later, with progression of prostate cancer and liver and lung metastases. Serum levels of neuron-specific enolase and pro-gastrinreleasing peptide (tumor markers) were elevated. He underwent re-biopsy of the prostate, and histopathological examination revealed small cell carcinoma. He was initially treated with carboplatin and etoposide therapy. Liver metastases showed partial remission, and serum tumor marker levels were temporarily reduced. However, disease progression was observed after 4 chemotherapy cycles, and he was then treated with an 8-cycle course of amrubicin. Metastases showed shrinkage, and serum tumor marker levels were reduced after 2 chemotherapy cycles. Tumor enlargement recurred after 8 cycles, and the patient is being treated with palliative therapy. Amrubicin therapy may be effective in the treatment of small cell carcinoma of the prostate.


Assuntos
Carcinoma de Células Pequenas , Neoplasias da Próstata , Idoso , Antagonistas de Androgênios , Antraciclinas , Humanos , Masculino , Recidiva Local de Neoplasia , Antígeno Prostático Específico
5.
Am J Cardiol ; 127: 163-168, 2020 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-32444028

RESUMO

Anthracycline-induced cardiotoxicity can lead to clinical and subclinical heart failure. Decrease of global longitudinal strain is a predictor for heart failure. Early detection of subclinical cardiotoxicity is crucial for timely intervention and prevention of further progression. Cardiac function of 41 survivors of childhood acute lymphoblastic leukemia (ALL) was assessed. Values of cardiac troponin T, N-terminal-pro-brain natriuretic peptide, conventional and myocardial 2D strain echocardiography were measured before (T = 0), during (T = 1, cumulative dose of 120 mg/m2), shortly after (T = 2) and long after anthracycline treatment (T = 3, ≥5 years after anthracycline exposure). Cardiac function of survivors at the latest follow up was compared with 70 healthy age-matched controls. None of the survivors showed clinical signs of cardiac failure at T = 3. Strain values decreased during anthracycline treatment and an ongoing reduction was seen at the latest follow-up (T = 3) with preserved cardiac function (normal ejection fraction and shortening fraction). At T = 1, a relative reduction in longitudinal strain (≥10% compared with baseline) was observed in 38% of the survivors, which increased to 54% at T=3. ALL survivors showed significantly lower conventional and myocardial 2D strain values, especially strain rate, compared with healthy age-matched controls. At T = 3, we did not find any abnormal cardiac troponin T levels. Six percent of the survivors showed abnormal N-terminal-pro-brain natriuretic peptide levels. This prospective study showed an ongoing reduction of 2D myocardial strain and strain rate, with preserved left ventricular ejection fraction (≤10% decrease compared with baseline) in asymptomatic ALL survivors at late follow-up.


Assuntos
Antraciclinas/uso terapêutico , Ecocardiografia/métodos , Eletrocardiografia , Cardiopatias/fisiopatologia , Contração Miocárdica/fisiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adolescente , Criança , Pré-Escolar , Feminino , Seguimentos , Cardiopatias/diagnóstico , Cardiopatias/etiologia , Humanos , Masculino , Países Baixos/epidemiologia , Projetos Piloto , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida/tendências , Fatores de Tempo
6.
Cancer Sci ; 111(7): 2579-2587, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32378780

RESUMO

We performed a genome-wide association study to investigate the association between single nucleotide polymorphisms and anthracycline-induced cardiotoxicity (ACT) in patients diagnosed with early breast cancer. From January 2000 to December 2015, 8490 patients underwent breast surgery at the National Cancer Center in Korea. Patients who received doxorubicin (cumulative dose 240 mg/m2 -300 mg/m2 ) with or without trastuzumab as a neoadjuvant/adjuvant therapy were included in our cohort. Sixty-seven patients in our cohort were diagnosed with ACT. Clinical data, including age, body weight, height, cancer stage, trastuzumab treatment, comorbidities, and concomitant medications, were collected retrospectively. Patients were classified as having either persistent or transient ACT based on their clinical course. In total, 346 946 single nucleotide polymorphisms in 42 cases and 215 controls were tested in this study. Body mass index (BMI) ≥25 kg/m2 [odds ratio (OR) = 2.45, 95% confidence interval (CI), 1.23-4.88, P = .011] and trastuzumab use (OR = 2.40, 95% CI, 1.11-5.17, P = .026) were identified as significant risk factors. We found 7 genetic variants for ACT including rs17530621 (SHISA3, P = 3.10E-06), rs11894115 (MPP4, P = 4.71E-06), rs58328254 (RPL7, P = 6.09E-06), and rs117299725 (PRUNE2, P = 8.53E-06), although none of these variants reached the Bonferroni-corrected significance level when adjusted for BMI and trastuzumab use ( = α1.44E-07 based on 0.05/346 946). rs117299725 was a common variant when only the persistent ACT group was analyzed separately. It is meaningful that our study analyzed comprehensively the influence of genetic variation on ACT, along with some clinical factors in Asian breast cancer patients who received anthracycline with or without trastuzumab. Further research will be needed on candidate genetic variants found in this study.


Assuntos
Antraciclinas/efeitos adversos , Neoplasias da Mama/complicações , Neoplasias da Mama/genética , Cardiotoxicidade/etiologia , Predisposição Genética para Doença , Variação Genética , Estudo de Associação Genômica Ampla , Antraciclinas/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/epidemiologia , Cardiotoxicidade/diagnóstico , Cardiotoxicidade/epidemiologia , Estudos de Casos e Controles , Comorbidade , Feminino , Estudos de Associação Genética/métodos , Humanos , Razão de Chances , Polimorfismo de Nucleotídeo Único , Vigilância da População , República da Coreia
7.
Toxicol Appl Pharmacol ; 399: 115038, 2020 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-32417440

RESUMO

The cardiotoxicity caused by doxorubicin and extravasation injury caused by anthracyclines is reduced by the clinically approved bisdioxopiperazine drug dexrazoxane. Dexrazoxane is a rings-closed analog of EDTA and is hydrolyzed in vivo to a form that strongly binds iron. Its protective effects were originally thought to be due to the ability of its metabolite to remove iron from the iron-doxorubicin complex, thereby preventing oxygen radical damage to cellular components. More recently it has been suggested that dexrazoxane may exert its protective effects by inhibiting topoisomerase IIß in the heart and inducing a reduction in its protein levels through induction of proteasomal degradation. The ability of dexrazoxane, other bisdioxopiperazines, and mitindomide to protect against doxorubicin-induced damage was determined in primary neonatal rat myocytes. This QSAR study showed that the protection that a series of bisdioxopiperazine analogs of dexrazoxane and the bisimide mitindomide offered against doxorubicin-induced myocyte damage was highly correlated with the ability of these compounds to catalytically inhibit the decatenation activity of topoisomerase II. The structural features of the dexrazoxane analogs that contribute to the binding and inhibition of topoisomerase II have been identified. These results suggest that the inhibition of topoisomerase II in myocytes by dexrazoxane is central to its role in its activity as an anthracycline cardioprotective agent. Additionally, sequence identity analysis of the amino acids surrounding the dexrazoxane binding site showed extremely high identity, not only between both invertebrate topoisomerase II isoforms, but also with yeast topoisomerase II as well.


Assuntos
Cardiotônicos/farmacologia , DNA Topoisomerases Tipo II/metabolismo , Dexrazoxano/farmacologia , Doxorrubicina/farmacologia , Miócitos Cardíacos/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Inibidores da Topoisomerase II/farmacologia , Animais , Antraciclinas/farmacologia , Feminino , Isoindóis/farmacologia , Masculino , Miócitos Cardíacos/metabolismo , Relação Quantitativa Estrutura-Atividade , Ratos , Ratos Sprague-Dawley
8.
PLoS One ; 15(5): e0233037, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32401825

RESUMO

Tumor-infiltrating lymphocyte (TIL) levels have prognostic and predictive values in treatment-naïve breast cancers. However, there have been controversies regarding TIL subset changes and their clinical implications in post-treatment breast cancers. This study aimed to explore change and prognostic significance of TIL subset infiltration after primary systemic therapy (PST) in breast cancer. One-hundred-fifty-five patients who had residual disease after anthracycline- or anthracycline plus taxane-based PST were included. The quantities of intratumoral and stromal TIL subsets (CD8+, CD4+, and FOXP3+ TILs) in pre- and post-PST breast cancer samples, as well as changes between them, were analyzed along with their correlations with clinicopathologic features and outcome of patients. As a whole, intratumoral CD8+ and CD4+ TILs increased after PST while stromal TILs decreased. Both intratumoral and stromal FOXP3+ TILs decreased after PST. The chemo-sensitive group [residual cancer burden (RCB) class I and II] showed the same pattern of change in intratumoral CD8+ TILs as the whole group, whereas the chemo-resistant group (RCB class III) showed no significant change in intratumoral CD8+ TIL infiltration after PST. Survival analyses for each TIL subset as well as their ratios revealed that high levels of intratumoral, stromal, and total CD8+ TIL infiltration after PST were independent predictors of longer patient survival. In subgroup analyses, CD8+ TIL infiltration after PST revealed prognostic significance in the chemo-resistant group but not in the chemo-sensitive group. In conclusion, infiltration of CD8+, CD4+, and FOXP3+ TIL changed after PST in the intratumoral and stromal compartments. Especially, increase of intratumoral CD8+ TILs was associated with chemo-responsiveness. Moreover, CD8+ TIL status in residual tumors after PST may be used as a potential prognostic marker in breast cancer patients who receive PST and provide additional prognostic information to chemo-resistant group.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Antígenos CD4/metabolismo , Antígenos CD8/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Linfócitos do Interstício Tumoral/imunologia , Adulto , Idoso , Antraciclinas/uso terapêutico , Neoplasias da Mama/imunologia , Neoplasias da Mama/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasia Residual , Prognóstico , Análise de Sobrevida , Taxoides/uso terapêutico , Resultado do Tratamento
9.
J Pharmacol Exp Ther ; 373(3): 402-415, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32253261

RESUMO

Bisdioxopiperazine agent dexrazoxane (ICRF-187) has been the only effective and approved drug for prevention of chronic anthracycline cardiotoxicity. However, the structure-activity relationships (SARs) of its cardioprotective effects remain obscure owing to limited investigation of its derivatives/analogs and uncertainties about its mechanism of action. To fill these knowledge gaps, we tested the hypothesis that dexrazoxane derivatives exert cardioprotection via metal chelation and/or modulation of topoisomerase IIß (Top2B) activity in chronic anthracycline cardiotoxicity. Dexrazoxane was alkylated in positions that should not interfere with the metal-chelating mechanism of cardioprotective action; that is, on dioxopiperazine imides or directly on the dioxopiperazine ring. The protective effects of these agents were assessed in vitro in neonatal cardiomyocytes. All studied modifications of dexrazoxane molecule, including simple methylation, were found to abolish the cardioprotective effects. Because this challenged the prevailing mechanistic concept and previously reported data, the two closest derivatives [(±)-4,4'-(propane-1,2-diyl)bis(1-methylpiperazine-2,6-dione) and 4-(2-(3,5-dioxopiperazin-1-yl)ethyl)-3-methylpiperazine-2,6-dione] were thoroughly scrutinized in vivo using a rabbit model of chronic anthracycline cardiotoxicity. In contrast to dexrazoxane, both compounds failed to protect the heart, as demonstrated by mortality, cardiac dysfunction, and myocardial damage parameters, although the pharmacokinetics and metal-chelating properties of their metabolites were comparable to those of dexrazoxane. The loss of cardiac protection was shown to correlate with their abated potential to inhibit and deplete Top2B both in vitro and in vivo. These findings suggest a very tight SAR between bisdioxopiperazine derivatives and their cardioprotective effects and support Top2B as a pivotal upstream druggable target for effective cardioprotection against anthracycline cardiotoxicity. SIGNIFICANCE STATEMENT: This study has revealed the previously unexpected tight structure-activity relationships of cardioprotective effects in derivatives of dexrazoxane, which is the only drug approved for the prevention of cardiomyopathy and heart failure induced by anthracycline anticancer drugs. The data presented in this study also strongly argue against the importance of metal-chelating mechanisms for the induction of this effect and support the viability of topoisomerase IIß as an upstream druggable target for effective and clinically translatable cardioprotection.


Assuntos
Antraciclinas/efeitos adversos , Cardiotoxicidade/tratamento farmacológico , DNA Topoisomerases Tipo II/metabolismo , Dexrazoxano/farmacologia , Coração/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Inibidores da Topoisomerase II/farmacologia , Animais , Cardiomiopatias/tratamento farmacológico , Cardiomiopatias/metabolismo , Linhagem Celular Tumoral , Células HL-60 , Humanos , Masculino , Modelos Animais , Miocárdio/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Coelhos , Ratos , Ratos Wistar , Relação Estrutura-Atividade
10.
J Surg Oncol ; 122(2): 164-169, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32291774

RESUMO

BACKGROUND AND OBJECTIVES: Marking positive lymph nodes (LNs) before neoadjuvant chemotherapy (NAC) may improve the accuracy of sentinel lymph node biopsy (SLNB). The aim of this study was to determine the feasibility of marking LNs with 4% carbon microparticle suspension (CMS) before NAC and to evaluate if this technique would improve the SLNB identification rate. METHODS: A prospective study of patients with cT1-T4, cN1-N2 breast cancer who underwent US-guided fine-needle aspiration biopsy (FNAB) of suspected LNs and concomitant marking with 4% CMS was performed. After NAC, LNs marked with 4% CMS and those marked with Patent Blue V dye (PBV) were identified and resected. RESULTS: Of the 123 patients included, 74 (60.1%) had positive LNs at FNAB. During axillary surgery, 4% CMS was identified in 121 of 123 patients (98.3%) and blue sentinel LNs in 91% (112 of 123 patients) (P = .0103). Comparing isolated results of PBV and 4%CMS + PBV, the association was better in identifying positive LNs (72.2% vs 97.7%) (P = .02). CONCLUSION: The association of 4% CMS and PBV is feasible and significantly increased the identification rate of positive LNs. 4% CMS may play an important role as a complementary technique in patients submitted to NAC.


Assuntos
Neoplasias da Mama/patologia , Carbono/administração & dosagem , Linfonodo Sentinela/patologia , Antraciclinas/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Biópsia por Agulha Fina/métodos , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Quimioterapia Adjuvante , Feminino , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Tamanho da Partícula , Estudos Prospectivos , Linfonodo Sentinela/diagnóstico por imagem , Taxoides/administração & dosagem
11.
PLoS One ; 15(4): e0231223, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32298286

RESUMO

We observed prominent effects of doxorubicin (Dox), an anthracycline widely used in anti-cancer therapy, on the aggregation and intracellular distribution of both partners of the H2A-H2B dimer, with marked differences between the two histones. Histone aggregation, assessed by Laser Scanning Cytometry via the retention of the aggregates in isolated nuclei, was observed in the case of H2A. The dominant effect of the anthracycline on H2B was its massive accumulation in the cytoplasm of the Jurkat leukemia cells concomitant with its disappearance from the nuclei, detected by confocal microscopy and mass spectrometry. A similar effect of the anthracycline was observed in primary human lymphoid cells, and also in monocyte-derived dendritic cells that harbor an unusually high amount of H2B in their cytoplasm even in the absence of Dox treatment. The nucleo-cytoplasmic translocation of H2B was not affected by inhibitors of major biochemical pathways or the nuclear export inhibitor leptomycin B, but it was completely diminished by PYR-41, an inhibitor with pleiotropic effects on protein degradation pathways. Dox and PYR-41 acted synergistically according to isobologram analyses of cytotoxicity. These large-scale effects were detected already at Dox concentrations that may be reached in the typical clinical settings, therefore they can contribute both to the anti-cancer mechanism and to the side-effects of this anthracycline.


Assuntos
Citoplasma/metabolismo , Doxorrubicina/farmacologia , Histonas/metabolismo , Transporte Ativo do Núcleo Celular , Antraciclinas/farmacologia , Antineoplásicos/farmacologia , Núcleo Celular/metabolismo , Proliferação de Células , Ácidos Graxos Insaturados/metabolismo , Humanos , Células Jurkat , Citometria de Varredura a Laser , Espectrometria de Massas , Microscopia Confocal , Monócitos/citologia
12.
Am J Cardiol ; 125(12): 1906-1912, 2020 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-32331711

RESUMO

To determine the impact of radiation therapy (XRT) in addition to trastuzumab (TZB) adjuvant chemotherapy for HER2+ breast cancer on left ventricular systolic function, we assessed demographics, oncologic treatment history including XRT exposure, and serial measurements of left ventricular ejection fraction (LVEF) in 135 consecutively identified women receiving TZB for treatment of adjuvant breast cancer. Longitudinal mixed effects models were fit to identify baseline to treatment changes in LVEF among those receiving TZB with or without concomitant anthracycline or XRT. Women averaged 53 ± 3 years in age, 77% were white, 62% patients had 1 or more cardiovascular risk factors at baseline, and mean duration of TZB was 11 ± 5 months. Seventy-seven women were treated with XRT and received between 4000 and 5500 cGy of radiation. The LVEF declined by an average of 3.4% after 1 year for those in the study. Relative to baseline upon completion of adjuvant TZB, LVEF remained reduced for those receiving anthracycline with or without XRT (p=0.002 for both), or XRT alone (p=0.002), but not in those without these therapies. Amongst patients treated only with XRT and TZB, LVEF declined 3.1% on average in those with left-sided disease and 6.9% on average in those with right-sided disease (p= 0.06, p= 0.008 respectively). Among women receiving TZB for adjuvant treatment of HER-2 positive breast cancer, the administration of XRT, anthracycline, or the combination of the 2 is associated with a persistent post-treatment as opposed to a temporary treatment related decline in LVEF.


Assuntos
Antraciclinas/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/radioterapia , Doenças Cardiovasculares/etiologia , Volume Sistólico , Trastuzumab/uso terapêutico , Quimioterapia Adjuvante , Feminino , Humanos , Pessoa de Meia-Idade , Receptor ErbB-2 , Fatores de Risco , Volume Sistólico/efeitos dos fármacos , Volume Sistólico/efeitos da radiação
13.
Anticancer Res ; 40(4): 2303-2309, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32234930

RESUMO

BACKGROUND/AIM: To predict pCR during neoadjuvant chemotherapy is still difficult. The aim of this study was to evaluate the optimal tumor reduction rate and modalities for predicting pCR after two cycles of docetaxel. PATIENTS AND METHODS: We analyzed 52 patients with HER2-positive or triple-negative breast cancer. The tumor reduction rate was evaluated after two 3-week cycles of docetaxel (plus trastuzumab for HER2-positive cancer patients). Patients without progression completed two additional cycles of docetaxel and four cycles of an anthracycline-containing regimen. RESULTS: Twenty-eight patients achieved pCR. The optimal tumor reduction rates for predicting pCR were 23, 39, 32, and 40% for US, caliper, MMG, and MRI measurements, respectively. The AUC was highest for caliper measurements. The optimal modality for predicting pCR differed among subtypes. CONCLUSION: Although tumor reduction rate after two cycles of chemotherapy is highly predictive of pCR, the optimal cutoff value differed among the modalities and breast cancer subtype.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Mama/efeitos dos fármacos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Adulto , Antraciclinas/administração & dosagem , Mama/diagnóstico por imagem , Mama/patologia , Neoplasias da Mama/metabolismo , Docetaxel/administração & dosagem , Esquema de Medicação , Feminino , Humanos , Imagem por Ressonância Magnética , Pessoa de Meia-Idade , Terapia Neoadjuvante , Receptor ErbB-2/metabolismo , Indução de Remissão , Trastuzumab/administração & dosagem , Carga Tumoral/efeitos dos fármacos , Ultrassonografia
14.
Klin Lab Diagn ; 65(3): 141-148, 2020.
Artigo em Russo | MEDLINE | ID: mdl-32163687

RESUMO

Anthracyclines are effectively used in many therapeutic regimens for breast cancer (BC). However, the dose-dependent cardiotoxic effect causes certain limitations on their use. Laboratory tests for risk prediction and early diagnosis of anthracycline-induced cardiotoxicity (ACIC) based on measuring the activity and concentration of topoisomerase 2ß, the levels of troponins T and I (TnT и TnI), N-terminal fragment of brain natriuretic peptide progenitor, remain relevant, but complicate the risk stratification with low specificity. Recently, the number of works devoted to the study of new biomarkers ACIC has been growing: galectin-3, soluble ST-2 (sST-2), and myeloperoxidase (MPO). In this review we analyzed current understanding of the classical markers ACIC and the results of recent studies dedicated to new predictors.


Assuntos
Antraciclinas/toxicidade , Neoplasias da Mama/tratamento farmacológico , Cardiotoxicidade , Antraciclinas/uso terapêutico , Biomarcadores , DNA Topoisomerases Tipo II , Detecção Precoce de Câncer , Feminino , Galectina 3 , Humanos , Proteína 1 Semelhante a Receptor de Interleucina-1 , Peptídeo Natriurético Encefálico , Peroxidase , Troponina I , Troponina T
15.
Medicine (Baltimore) ; 99(11): e19566, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32176115

RESUMO

Chemotherapy may cause ovarian toxicity and infertility. Cancer patients are usually overwhelmed, and focus exclusively on cancer diagnosis and may not pay attention to fertility-related issues. In this paper we look at the rate of amenorrhea and fertility counseling among such young patients.Premenopausal women with early-stage breast cancer treated with adjuvant or neoadjuvant chemotherapy were recruited. Amenorrhea was defined as absence of menstruation for ≥12 months after the completion of chemotherapy.A total of 94 patients met the eligibility criteria and were included in this analysis. Median age at diagnosis was 35.7 (range, 22-44) years. Seventy-nine (85.9%) respondents were counseled about amenorrhea and 37 (40.2%) were considering having children. Long-term amenorrhea was reported by 51 (54.3%) patients. The addition of taxanes to anthracyclines, in 2 different regimens, increased the risk of amenorrhea to 69.2% and 66.7% compared to 38.9% with anthracycline-alone, P < .0001. Longer duration of chemotherapy (≥24 weeks) might also be associated with higher rate of amenorrhea (67.7%) compared to 43.4% in those who had shorter duration (<24 weeks), P = .031.The addition of taxanes to anthracycline-based chemotherapy increased the risk of amenorrhea. However, shorter duration of chemotherapy, even with taxanes, may lower such risk. Our study highlights the importance of fertility counseling to improve fertility preservation rates. Given the importance of taxanes, shorter regimens are associated with lower amenorrhea rates and should be preferred over longer ones.


Assuntos
Amenorreia/induzido quimicamente , Antraciclinas/efeitos adversos , Antineoplásicos/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Preservação da Fertilidade , Taxoides/efeitos adversos , Adulto , Neoplasias da Mama/patologia , Quimioterapia Adjuvante/efeitos adversos , Aconselhamento , Feminino , Humanos , Jordânia , Estadiamento de Neoplasias , Estudos Retrospectivos , Adulto Jovem
16.
Heart Fail Clin ; 16(2): 231-241, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32143767

RESUMO

Several cancer treatments cause cardiotoxicity that can lead to heart failure, coronary artery disease, arrhythmia, and pericardial disease. In this review, representative cases of heart failure following cardiotoxicity caused by trastuzumab, anthracycline, and hematopoietic stem cell transplantation are described with case notes. Additionally, other important points regarding cardiotoxicity related to heart failure are reported. During and after potentially cardiotoxic therapy, periodic cardiac examinations are recommended to detect any cardiovascular disorders; these are ameliorated if appropriately diagnosed at an earlier stage. It is important for cardiologists and oncologists to understand the pathophysiology of representative cardiovascular disease cases following cancer treatment.


Assuntos
Antraciclinas/farmacologia , Insuficiência Cardíaca , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Neoplasias/tratamento farmacológico , Trastuzumab/farmacologia , Antineoplásicos/farmacologia , Cardiotoxicidade , Monitoramento de Medicamentos/métodos , Insuficiência Cardíaca/induzido quimicamente , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos
17.
Ann Afr Med ; 19(1): 1-7, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32174608

RESUMO

We report three cases of heart failure (HF) associated with the use of cytotoxic drugs such as anthracycline, cyclophosphamide, and 5-fluorouracil in the treatment of breast cancer in Nigerians. The patients had systolic and diastolic HF: HF with reduced ejection fraction and preserved ejection fraction. The prevalence of breast cancer is increasing across Africa, and cytotoxics are some of the most common and best drugs used during management. The cardiotoxicity caused by these drugs limits their use as chemotherapeutic agents. Cytotoxic-induced HF is a preventable and manageable cause of cardiovascular disease (CVD) in Nigeria and Africa. This article discusses the pathophysiology of cytotoxic-induced HF and presents the risk factors that impair cardiovascular function. The importance of proper assessment and the prophylactic and therapeutic measures in the management of cytotoxic-induced HF are emphasized. The peculiar challenges in the management of cytotoxic-induced HF in Nigeria were also discussed. The need for early involvement of cardiologists by oncologists to improve on the chemotherapeutic and cardiovascular outcome in the management of patients with breast cancer was stressed. Perhaps, it is time to birth a new discipline of cardiooncology in Nigeria.


Assuntos
Antraciclinas/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Ciclofosfamida/efeitos adversos , Fluoruracila/efeitos adversos , Insuficiência Cardíaca/induzido quimicamente , Idoso , Antraciclinas/uso terapêutico , Cardiotoxicidade , Ciclofosfamida/uso terapêutico , Feminino , Fluoruracila/uso terapêutico , Humanos , Pessoa de Meia-Idade
18.
Anticancer Res ; 40(3): 1571-1578, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32132059

RESUMO

BACKGROUND/AIM: The efficacy of the combination of amrubicin and bevacizumab against advanced non small-cell lung cancer (NSCLC), as a second or third-line treatment, was evaluated. PATIENTS AND METHODS: Amrubicin was administered for 3 days to patients with previously treated advanced NSCLC, whereas bevacizumab was administered on day 1 of each cycle; this regimen was repeated every 3 weeks. RESULTS: Among the 16 patients, an overall response rate of 12.5% (for two patients) was achieved, and the overall disease control rate was 93.7%. Progression free survival and overall survival were 8.5 and 16.6 months, respectively. Grade 3 or 4 haematological toxicities were leukopenia, neutropenia, and febrile neutropenia. Grade 3 proteinuria and infection were the non haematological adverse events. CONCLUSION: The combination of amrubicin and bevacizumab is a promising regimen in the second or third-line treatment for advanced non-squamous NSCLC; however, physicians must recognise the risk of proteinuria related with this regimen.


Assuntos
Antraciclinas/uso terapêutico , Antineoplásicos/uso terapêutico , Bevacizumab/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Idoso , Antraciclinas/farmacologia , Antineoplásicos/farmacologia , Bevacizumab/farmacologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Estudos de Viabilidade , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
19.
J Surg Res ; 250: 143-147, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32044511

RESUMO

BACKGROUND: A subgroup of triple-negative breast cancer (TNBC) shows impaired BRCA1 function owing to causes other than mutation, which is called "BRCAness." DNA-damaging agents are known to have more efficacy in BRCA1-mutant tumors than mitotic poisons. We conducted a prospective single-arm clinical trial of neoadjuvant chemotherapy (NAC) using an anthracycline-based regimen without taxanes for BRCAness TNBCs. MATERIALS AND METHODS: BRCAness was examined using the multiplex ligation-dependent probe amplification (MLPA) method in TNBC cases. For BRCAness cases, NAC was performed with anthracycline-based regimens without additional taxanes. RESULTS: A total of 30 patients with TNBC were enrolled. MLPA was successfully performed in 25 patients. Eighteen patients (72%) showed BRCAness. Twenty-three patients received NAC as per the protocol. On analysis, the clinical response rate (complete response plus partial response) was 76.4%, and the pathological complete response rate was 35.3%. CONCLUSIONS: The interim analysis revealed that the pathological complete response rate was lower than estimated. Therefore, BRCAness by MLPA was not sufficient to predict the therapeutic response to anthracycline-based regimens in TNBC.


Assuntos
Antraciclinas/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Proteína BRCA1/metabolismo , Terapia Neoadjuvante/métodos , Neoplasias de Mama Triplo Negativas/terapia , Adulto , Idoso , Proteína BRCA1/análise , Quimioterapia Adjuvante/métodos , Ciclofosfamida/uso terapêutico , Docetaxel/uso terapêutico , Epirubicina/uso terapêutico , Feminino , Fluoruracila/uso terapêutico , Humanos , Mastectomia , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Resultado do Tratamento , Neoplasias de Mama Triplo Negativas/patologia
20.
Circ Cardiovasc Qual Outcomes ; 13(3): e005984, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32106704

RESUMO

BACKGROUND: The National Comprehensive Cancer Network and American Society of Clinical Oncology recommend consideration of the use of echocardiography 6 to 12 months after completion of anthracycline-based chemotherapy in at-risk populations. Assessment of BNP (B-type natriuretic peptide) has also been suggested by the American College of Cardiology/American Heart Association/Heart Failure Society of America for the identification of Stage A (at risk) heart failure patients. The real-world frequency of the use of these tests in patients after receipt of anthracycline therapy, however, has not been studied previously. METHODS AND RESULTS: In this retrospective study, using administrative claims data from the OptumLabs Data Warehouse, we identified 31 447 breast cancer and lymphoma patients (age ≥18 years) who were treated with an anthracycline in the United States between January 1, 2008 and January 31, 2018. Continuous medical and pharmacy coverage was required for at least 6 months before the initial anthracycline dose and 12 months after the final dose. Only 36.1% of patients had any type of cardiac surveillance (echocardiography, BNP, or cardiac imaging) in the year following completion of anthracycline therapy (29.7% echocardiography). Surveillance rate increased from 37.5% in 2008 to 42.7% in 2018 (25.6% in 2008 to 40.5% echocardiography in 2018). Lymphoma patients had a lower likelihood of any surveillance compared with patients with breast cancer (odds ratio, 0.79 [95% CI, 0.74-0.85]; P<0.001). Patients with preexisting diagnoses of coronary artery disease and arrhythmia had the highest likelihood of cardiac surveillance (odds ratio, 1.54 [95% CI, 1.39-1.69] and odds ratio, 1.42 [95% CI, 1.3-1.53]; P<0.001 for both), although no single comorbidity was associated with a >50% rate of surveillance. CONCLUSIONS: The majority of survivors of breast cancer and lymphoma who have received anthracycline-based chemotherapy do not undergo cardiac surveillance after treatment, including those with a history of cardiovascular comorbidities, such as heart failure.


Assuntos
Antraciclinas/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Sobreviventes de Câncer , Ecocardiografia/tendências , Cardiopatias/diagnóstico por imagem , Linfoma/tratamento farmacológico , Padrões de Prática Médica/tendências , Demandas Administrativas em Assistência à Saúde , Adolescente , Adulto , Idoso , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/epidemiologia , Data Warehousing , Feminino , Fidelidade a Diretrizes/tendências , Cardiopatias/induzido quimicamente , Cardiopatias/epidemiologia , Humanos , Linfoma/diagnóstico , Linfoma/epidemiologia , Masculino , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Valor Preditivo dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Estados Unidos/epidemiologia , Adulto Jovem
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