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1.
Lancet Oncol ; 24(9): 1029-1041, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37657462

RESUMO

BACKGROUND: The development of more potent selective oestrogen receptor antagonists and degraders (SERDs) that can be orally administered could help to address the limitations of current endocrine therapies. We report the primary and final analyses of the coopERA Breast Cancer study, designed to test whether giredestrant, a highly potent, non-steroidal, oral SERD, would show a stronger anti-proliferative effect than anastrozole after 2 weeks for oestrogen receptor-positive, HER2-negative, untreated early breast cancer. METHODS: In this open-label, randomised, controlled, phase 2 study, postmenopausal women were eligible if they were aged 18 years or older; had clinical T stage (cT)1c to cT4a-c (≥1·5 cm within cT1c) oestrogen receptor-positive, HER2-negative, untreated early breast cancer; an Eastern Cooperative Oncology Group performance status of 0-1; and baseline Ki67 score of at least 5%. The study was conducted at 59 hospital or clinic sites in 11 countries globally. Participants were randomly assigned (1:1) to giredestrant 30 mg oral daily or anastrozole 1 mg oral daily on days 1-14 (window-of-opportunity phase) via an interactive web-based system with permuted-block randomisation with block size of four. Randomisation was stratified by cT stage, baseline Ki67 score, and progesterone receptor status. A 16-week neoadjuvant phase comprised the same regimen plus palbociclib 125 mg oral daily on days 1-21 of a 28-day cycle, for four cycles. The primary endpoint was geometric mean relative Ki67 score change from baseline to week 2 in patients with complete central Ki67 scores at baseline and week 2 (window-of-opportunity phase). Safety was assessed in all patients who received at least one dose of study drug. The study is registered with ClinicalTrials.gov (NCT04436744) and is complete. FINDINGS: Between Sept 4, 2020, and June 22, 2021, 221 patients were enrolled and randomly assigned to the giredestrant plus palbociclib group (n=112; median age 62·0 years [IQR 57·0-68·5]) or anastrozole plus palbociclib group (n=109; median age 62·0 [57·0-67·0] years). 15 (7%) of 221 patients were Asian, three (1%) were Black or African American, 194 (88%) were White, and nine (4%) were unknown races. At data cutoff for the primary analysis (July 19, 2021), the geometric mean relative reduction of Ki67 from baseline to week 2 was -75% (95% CI -80 to -70) with giredestrant and -67% (-73 to -59) with anastrozole (p=0·043), meeting the primary endpoint. At the final analysis (data cutoff Nov 24, 2021), the most common grade 3-4 adverse events were neutropenia (29 [26%] of 112 in the giredestrant plus palbociclib group vs 29 [27%] of 109 in the anastrozole plus palbociclib group) and decreased neutrophil count (17 [15%] vs 16 [15%]). Serious adverse events occurred in five (4%) patients in the giredestrant plus palbociclib group and in two (2%) patients in the anastrozole plus palbociclib group. There were no treatment-related deaths. One patient died due to an adverse event in the giredestrant plus palbociclib group (myocardial infarction). INTERPRETATION: Giredestrant offers encouraging anti-proliferative and anti-tumour activity and was well tolerated, both as a single agent and in combination with palbociclib. Results justify further investigation in ongoing trials. FUNDING: F Hoffmann-La Roche.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Pessoa de Meia-Idade , Anastrozol , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Receptores de Estrogênio , Terapia Neoadjuvante/efeitos adversos , Antígeno Ki-67
2.
J Oncol Pharm Pract ; 29(7): 1793-1796, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37455486

RESUMO

INTRODUCTION: Drug-induced subacute cutaneous lupus erythematosus (DI-SCLE) has been associated with drugs with different mechanisms of action, including anti-hypertensives, tumour necrosis factor-α inhibitors and even some chemotherapy medicines. In the last years, a few reports have been described in patients treated with cyclin-dependent kinase (CDK) 4/6 inhibitors, palbociclib and abemaciclib. CASE REPORT: Here, we describe a case of DI-SCLE in association with ribociclib and exemestane in a woman diagnosed with metastatic breast cancer. MANAGEMENT AND OUTCOME: Topical mometasone was prescribed for two weeks with complete resolution of lesions, also abemaciclib was substituted for ribociclib, and the patient had stable disease with no relapse of DI-SCLE. DISCUSSION: To our knowledge, this is the first report of ribociclib-induced SCLE but based on the DI-SCLE reported cases associated others CDK4/6 inhibitors, the role of this family of drugs in dermatopathology must be further investigated.


Assuntos
Neoplasias da Mama , Lúpus Eritematoso Cutâneo , Feminino , Humanos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Recidiva Local de Neoplasia , Lúpus Eritematoso Cutâneo/induzido quimicamente , Lúpus Eritematoso Cutâneo/patologia
4.
Monaldi Arch Chest Dis ; 92(4)2022 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-35179011

RESUMO

Trastuzumab therapy has dramatically changed breast cancer prognosis. Consensus documents recommend a close monitoring during therapy, not always feasible, especially in metastatic breast cancer. The purpose of this study is to describe trastuzumab cardiotoxicity in metastatic breast cancer patients to understand how to improve cardiovascular monitoring. We retrospectively studied metastatic breast cancer patients scheduled for trastuzumab therapy (2001-2018). All patients underwent a baseline evaluation and monitoring during therapy. Cardiotoxicity was defined as symptomatic heart failure or asymptomatic decrease in left ventricular ejection fraction > 10% from baseline and < 53%. Ninety-two women were included, mean age 61 years (±14.43), median follow-up 42.5 months (IQR 26-74). Fourteen percent developed cardiotoxicity:  two heart failure with preserved left ventricular ejection fraction, three heart failure with reduced left ventricular ejection fraction, and eight asymptomatic decreased in left ventricular ejection fraction. Eighty-one percent of cardiac dysfunction cases occurred within the first 4 years and on median of 31 months from trastuzumab initiation. Thus, in metastatic breast cancer patients, trastuzumab-mediated cardiotoxicity occurred more frequently during the first 4 years. These data should be considered to optimize follow-up protocols.


Assuntos
Neoplasias da Mama , Cardiopatias , Insuficiência Cardíaca , Neoplasias da Mama/tratamento farmacológico , Cardiotoxicidade/epidemiologia , Cardiotoxicidade/etiologia , Feminino , Cardiopatias/complicações , Insuficiência Cardíaca/complicações , Humanos , Incidência , Pessoa de Meia-Idade , Receptor ErbB-2 , Estudos Retrospectivos , Volume Sistólico , Trastuzumab/efeitos adversos , Função Ventricular Esquerda
5.
Eur J Prev Cardiol ; 29(6): 859-868, 2022 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-33624069

RESUMO

AIMS: The actual usefulness of cardiovascular (CV) risk factor assessment in the prognostic evaluation of cancer patients treated with cardiotoxic treatment remains largely unknown. Prospective multicentre study in patients scheduled to receive anticancer therapy related with moderate/high cardiotoxic risk. METHODS AND RESULTS: A total of 1324 patients underwent follow-up in a dedicated cardio-oncology clinic from April 2012 to October 2017. Special care was given to the identification and control of CV risk factors. Clinical data, blood samples, and echocardiographic parameters were prospectively collected according to protocol, at baseline before cancer therapy and then at 3 weeks, 3 months, 6 months, 1 year, 1.5 years, and 2 years after initiation of cancer therapy. At baseline, 893 patients (67.4%) presented at least one risk factor, with a significant number of patients newly diagnosed during follow-up. Individual risk factors were not related with worse prognosis during a 2-year follow-up. However, a higher Systemic Coronary Risk Estimation (SCORE) was significantly associated with higher rates of severe cardiotoxicity (CTox) and all-cause mortality [hazard ratio (HR) 1.79 (95% confidence interval, CI 1.16-2.76) for SCORE 5-9 and HR 4.90 (95% CI 2.44-9.82) for SCORE ≥10 when compared with patients with lower SCORE (0-4)]. CONCLUSIONS: This large cohort of patients treated with a potentially cardiotoxic regimen showed a significant prevalence of CV risk factors at baseline and significant incidence during follow-up. Baseline CV risk assessment using SCORE predicted severe CTox and all-cause mortality. Therefore, its use should be considered in the evaluation of cancer patients.


Assuntos
Doenças Cardiovasculares , Neoplasias , Cardiotoxicidade , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Fatores de Risco de Doenças Cardíacas , Humanos , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Neoplasias/epidemiologia , Prevalência , Prognóstico , Estudos Prospectivos , Sistema de Registros , Fatores de Risco
6.
Eur Heart J ; 41(18): 1720-1729, 2020 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-32016393

RESUMO

AIM: Cardiotoxicity (CTox) is a major side effect of cancer therapies, but uniform diagnostic criteria to guide clinical and research practices are lacking. METHODS AND RESULTS: We prospectively studied 865 patients, aged 54.7 ± 13.9; 16.3% men, scheduled for anticancer therapy related with moderate/high CTox risk. Four groups of progressive myocardial damage/dysfunction were considered according to current guidelines: normal, normal biomarkers (high-sensitivity troponin T and N-terminal natriuretic pro-peptide), and left ventricular (LV) function; mild, abnormal biomarkers, and/or LV dysfunction (LVD) maintaining an LV ejection fraction (LVEF) ≥50%; moderate, LVD with LVEF 40-49%; and severe, LVD with LVEF ≤40% or symptomatic heart failure. Cardiotoxicity was defined as new or worsening of myocardial damage/ventricular function from baseline during follow-up. Patients were followed for a median of 24 months. Cardiotoxicity was identified in 37.5% patients during follow-up [95% confidence interval (CI) 34.22-40.8%], 31.6% with mild, 2.8% moderate, and 3.1% with severe myocardial damage/dysfunction. The mortality rate in the severe CTox group was 22.9 deaths per 100 patients-year vs. 2.3 deaths per 100 patients-year in the rest of groups, hazard ratio of 10.2 (95% CI 5.5-19.2) (P < 0.001). CONCLUSIONS: The majority of patients present objective data of myocardial injury/dysfunction during or after cancer therapy. Nevertheless, severe CTox, with a strong prognostic relationship, was comparatively rare. This should be reflected in protocols for clinical and research practices.


Assuntos
Disfunção Ventricular Esquerda , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Sistema de Registros , Volume Sistólico , Disfunção Ventricular Esquerda/induzido quimicamente , Disfunção Ventricular Esquerda/epidemiologia , Função Ventricular Esquerda
7.
Urol Oncol ; 30(4): 356-61, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-20207176

RESUMO

Renal cell carcinoma therapy has changed in a very significant way in the last few years. Up to 5 new agents have been developed, improving the results previously achieved with cytokine therapy. Bevacizumab, sorafenib, sunitinib, temsirolimus, and everolimus are now part of the therapeutic arsenal for this illness. Particularly, this has been the first tumoral type in which inhibition of mammalian target of rapamycin (mTOR) has proved its efficacy in phase III trials, either as first-line therapy for poor prognosis patients (temsirolimus, CCI-779) or as second-line therapy after failure of tyrosine-kinase inhibitors (everolimus, RAD001). In this paper, we review the basis for mTOR inhibition in RCC, and discuss the results of the trials involving temsirolimus and everolimus for the treatment of this disease.


Assuntos
Carcinoma de Células Renais/enzimologia , Neoplasias Renais/enzimologia , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Carcinoma de Células Renais/tratamento farmacológico , Ensaios Clínicos Fase III como Assunto , Everolimo , Humanos , Neoplasias Renais/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Sirolimo/análogos & derivados , Sirolimo/uso terapêutico , Serina-Treonina Quinases TOR/antagonistas & inibidores , Resultado do Tratamento
9.
Clin Transl Oncol ; 10(2): 111-6, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18258510

RESUMO

INTRODUCTION: Hepatic toxicity of breast cancer therapy is well known, usually consisting of elevation in the serum levels of hepatic enzymes or fatty infiltration of the liver. The chemotherapeutic agents most commonly linked to hepatotoxic effects are methotrexate, anthracyclines, taxanes and cyclophosphamide. There are few reports of patients with liver metastasis having radiological findings mimicking cirrhosis, both in the presence or the absence of prior systemic chemotherapy. Hepatotoxicity of antineoplastic drugs and cellular necrosis induced by response of liver metastases to chemotherapy may play a critical role in its physiopathology. MATERIALS AND METHODS: This article reports a series of ten women with breast cancer (nine with liver metastasis) treated with chemotherapy or hormonotherapy. RESULTS: They had low risk factors for hepatic disease, but developed a cirrhosis-like appearance in the computed tomography scan. The patient without liver metastasis is the second of this kind described in the literature. Relatively few reports have documented clinical sequelae of portal hypertension. In our series, three patients had oesophageal bleeding varices needing be hospitalised. To our knowledge, these are the first cases reported in the literature. CONCLUSIONS: This suggests that some manifestations of portal hypertension may develop in association with the cirrhosis- like pattern induced by breast cancer therapy.


Assuntos
Neoplasias da Mama/patologia , Cirrose Hepática/etiologia , Neoplasias Hepáticas/secundário , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Feminino , Humanos , Hipertensão Portal/etiologia , Hipertensão Portal/fisiopatologia , Cirrose Hepática/patologia , Neoplasias Hepáticas/tratamento farmacológico , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X
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