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1.
J Am Coll Cardiol ; 71(20): 2281-2290, 2018 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-29540327

RESUMO

BACKGROUND: Anthracycline (ANT) chemotherapy is associated with cardiotoxicity. Prevention with ß-blockers remains controversial. OBJECTIVES: This prospective, randomized, double-blind, placebo-controlled study sought to evaluate the role of carvedilol in preventing ANT cardiotoxicity. METHODS: The authors randomized 200 patients with HER2-negative breast cancer tumor status and normal left ventricular ejection fraction (LVEF) referred for ANT (240 mg/m2) to receive carvedilol or placebo until chemotherapy completion. The primary endpoint was prevention of a ≥10% reduction in LVEF at 6 months. Secondary outcomes were effects of carvedilol on troponin I, B-type natriuretic peptide, and diastolic dysfunction. RESULTS: Primary endpoint occurred in 14 patients (14.5%) in the carvedilol group and 13 patients (13.5%) in the placebo group (p = 1.0). No differences in changes of LVEF or B-type natriuretic peptide were noted between groups. A significant difference existed between groups in troponin I levels over time, with lower levels in the carvedilol group (p = 0.003). Additionally, a lower incidence of diastolic dysfunction was noted in the carvedilol group (p = 0.039). A nonsignificant trend toward a less-pronounced increase in LV end-diastolic diameter during the follow-up was noted in the carvedilol group (44.1 ± 3.64 mm to 45.2 ± 3.2 mm vs. 44.9 ± 3.6 mm to 46.4 ± 4.0 mm; p = 0.057). CONCLUSIONS: In this largest clinical trial of ß-blockers for prevention of cardiotoxicity under contemporary ANT dosage, the authors noted a 13.5% to 14.5% incidence of cardiotoxicity. In this scenario, carvedilol had no impact on the incidence of early onset of LVEF reduction. However, the use of carvedilol resulted in a significant reduction in troponin levels and diastolic dysfunction. (Carvedilol Effect in Preventing Chemotherapy-Induced Cardiotoxicity [CECCY]; NCT01724450).


Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Antineoplásicos/efeitos adversos , Cardiotoxicidade/diagnóstico por imagem , Cardiotoxicidade/prevenção & controle , Carvedilol/uso terapêutico , Adulto , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/epidemiologia , Cardiotoxicidade/epidemiologia , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos
2.
Rev. Assoc. Med. Bras. (1992) ; 63(9): 814-823, 2017. tab, graf
Artigo em Inglês | LILACS-Express | ID: biblio-896397

RESUMO

Summary Following decades of relative ostracism, advances in the treatment of melanoma have brought a new reality for patients, physicians and researchers. While antibodies targeting molecules involved in the modulation of the interaction between melanoma and immune cells changed the meaning of the term "cancer immunotherapy," a better characterization of the molecular aberrations involved in melanoma carcinogenesis prompted the development of inhibitors of the mitogen-activated protein kinase pathway (MAPK) that also led to significant improvements both in response rates and survival. As a result, new drugs have been approved for clinical use in the United States and Europe, including the immune-checkpoint blockers ipilmumab, pembrolizumab and nivolumab, the oncolytic herpesvirus talimogene laherparepvec, and the targeted-agents vemurafenib, dabrafenib, cobimetinib and trametinib. In this article, we review the results of studies that brought new approaches to the bedside and discuss how these developments are being incorporated into the care of patients in Brazil.


Resumo Após décadas de ostracismo, os recentes avanços no tratamento do melanoma trouxeram uma nova realidade para pacientes, médicos e pesquisadores. Enquanto anticorpos monoclonais voltados a moléculas envolvidas na modulação da interação entre células do melanoma e do sistema imune consolidaram o uso da "imunoterapia", um melhor conhecimento acerca das aberrações genômicas envolvidas na carcinogênese do melanoma viabilizaram o desenvolvimento de inibidores da via mitogen-activated protein kinase pathway (MAPK), o que também resultou em ganhos significativos em taxas de resposta e sobrevida. Consequentemente, novas modalidades de tratamento foram aprovadas para uso clínico nos Estados Unidos e na Europa, incluindo os bloqueadores de correceptores imunes ipilimumabe, nivolumabe e pembrolizumabe, o herpesvírus oncolítico talimogene laherparepvec (T-VEC), e os agentes-alvo vemurafenibe, dabrafenibe, cobimetinibe e trametinibe. Nesse artigo, revisamos os resultados que trouxeram novas alternativas para a prática clínica e discutimos a incorporação desses avanços ao cuidado de pacientes no Brasil.

3.
Rev Assoc Med Bras (1992) ; 63(9): 814-823, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29239458

RESUMO

Following decades of relative ostracism, advances in the treatment of melanoma have brought a new reality for patients, physicians and researchers. While antibodies targeting molecules involved in the modulation of the interaction between melanoma and immune cells changed the meaning of the term "cancer immunotherapy," a better characterization of the molecular aberrations involved in melanoma carcinogenesis prompted the development of inhibitors of the mitogen-activated protein kinase pathway (MAPK) that also led to significant improvements both in response rates and survival. As a result, new drugs have been approved for clinical use in the United States and Europe, including the immune-checkpoint blockers ipilmumab, pembrolizumab and nivolumab, the oncolytic herpesvirus talimogene laherparepvec, and the targeted-agents vemurafenib, dabrafenib, cobimetinib and trametinib. In this article, we review the results of studies that brought new approaches to the bedside and discuss how these developments are being incorporated into the care of patients in Brazil.


Assuntos
Antineoplásicos/administração & dosagem , Imunoterapia/métodos , Melanoma/tratamento farmacológico , Inibidores de Proteínas Quinases/administração & dosagem , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Humanos , Proteínas Proto-Oncogênicas B-raf/administração & dosagem
4.
Rare Tumors ; 5(3): e35, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24179647

RESUMO

The role of chemotherapy in well differentiated neuroendocrine tumors (NET) has been questioned. It was recently demonstrated that everolimus and sunitinib have activity in low and intermediate grade pancreatic NET. The aim of this study was to evaluate the activity of capecitabine and oxaliplatin (CapOx) combination in treating NET in an unselected population. In this regard, we retrospectively evaluated 24 patients diagnosed with metastatic NET treated with CapOx at two Brazilian institutes that are reference centers in cancer care. Tumor response was measured by RECIST criteria. Median age at diagnosis was 56 years, 71% had ECOG 0 or 1, the majority of tumors were primary from pancreas (67%) followed by lung (17%), and 29% were functional. According to WHO classification criteria, 25% were grade 1, 37.5% grade 2 and 37.5% grade 3. Most patients received CapOx as second-line therapy, with a median of 6 cycles. Twenty-nine percent of patients had partial response by RECIST criteria. No association was observed between response rate and tumor grade, primary site or line of CapOx. The median time to progression was 9.8 months and median time to treatment failure was 12.1 months. Seventy-five percent of patients are alive at the time of this analysis; therefore, median overall survival was not reached. The CapOx combination was shown to be active in an unselected population with metastatic NET and may be a good platform for the incorporation of the newer molecular targeted agents being investigated for the treatment of this entity.

5.
Future Oncol ; 8(7): 775-81, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22830398

RESUMO

Cediranib is a potent inhibitor of the VEGF family receptor tyrosine kinases, and a new agent in cancer treatment. The drug has shown promising activity in a variety of solid malignancies, in preclinical models and in clinical trials. Its pharmacokinetics allow for a convenient once-daily administration, with a toxicity profile that is very similar to other VEGF inhibitors. Its main side effects include hypertension, nausea, dysphonia, fatigue and diarrhea. Adverse events seem to be manageable, especially when used in doses lower than 45 mg/day. Studies have shown some activity as a single agent or in combination in advanced tumors, but not enough to secure its approval for routine use up to now. Clinical trials are still evaluating the role of cediranib in combination chemotherapy with cytotoxic agents.


Assuntos
Antineoplásicos/uso terapêutico , Inibidores Enzimáticos/uso terapêutico , Quinazolinas/farmacologia , Quinazolinas/uso terapêutico , Receptores Proteína Tirosina Quinases/antagonistas & inibidores , Animais , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacologia , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Neoplasias Colorretais/tratamento farmacológico , Ensaios de Seleção de Medicamentos Antitumorais , Inibidores Enzimáticos/efeitos adversos , Inibidores Enzimáticos/farmacologia , Feminino , Glioblastoma/tratamento farmacológico , Humanos , Neoplasias Renais/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias da Próstata/tratamento farmacológico , Quinazolinas/efeitos adversos , Sarcoma/tratamento farmacológico
6.
Support Care Cancer ; 13(10): 850-3, 2005 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-15838618

RESUMO

OBJECTIVES: Chemotherapy-induced nausea and vomiting (QTNV) are very uncomfortable symptoms for patients with cancer, which can be circumvented in most of them with drug combinations containing serotonin receptor antagonists (5-HT3 receptor antagonists) such as granisetron. In an attempt to decrease costs of QTNV prophylaxis, we studied a lower dose regimen of granisetron. PATIENTS AND METHODS: Sixty patients with cancer scheduled to receive moderately/highly emetogenic chemotherapy were pretreated 1 h before with 0.5 mg granisetron p.o. combined with dexamethasone 20 mg i.v. RESULTS: We observed complete control for nausea, vomiting, and nausea and vomiting in 78% [95% confidence interval (CI), 67-89%], 61% (95% CI, 47.5-74.5%), and 58% (95% CI, 44.3-71.7%) of the patients, respectively. This regimen was very well tolerated; headache (35%), xerostomia (11%), and constipation (5%) were the most frequent adverse symptoms reported. CONCLUSIONS: The regimen with lower dose granisetron is effective for acute QTNV prophylaxis and offers a cheaper alternative for QTNV control. We feel that these encouraging results should be confirmed in a randomized comparative trial.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Granisetron/administração & dosagem , Náusea/induzido quimicamente , Náusea/prevenção & controle , Antagonistas da Serotonina/administração & dosagem , Vômito/induzido quimicamente , Vômito/prevenção & controle , Adulto , Idoso , Brasil , Feminino , Granisetron/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Náusea/tratamento farmacológico , Neoplasias/tratamento farmacológico , Projetos Piloto , Antagonistas da Serotonina/uso terapêutico , Inquéritos e Questionários , Vômito/tratamento farmacológico
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