Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.188
Filtrar
1.
Lancet Oncol ; 22(4): 476-488, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33721561

RESUMO

BACKGROUND: The MINDACT trial showed excellent 5-year distant metastasis-free survival of 94·7% (95% CI 92·5-96·2) in patients with breast cancer of high clinical and low genomic risk who did not receive chemotherapy. We present long-term follow-up results together with an exploratory analysis by age. METHODS: MINDACT was a multicentre, randomised, phase 3 trial done in 112 academic and community hospitals in nine European countries. Patients aged 18-70 years, with histologically confirmed primary invasive breast cancer (stage T1, T2, or operable T3) with up to three positive lymph nodes, no distant metastases, and a WHO performance status of 0-1 were enrolled and their genomic risk (using the MammaPrint 70-gene signature) and clinical risk (using a modified version of Adjuvant! Online) were determined. Patients with low clinical and low genomic risk results did not receive chemotherapy, and patients with high clinical and high genomic risk did receive chemotherapy (mostly anthracycline-based or taxane-based, or a combination thereof). Patients with discordant risk results (ie, patients with high clinical risk but low genomic risk, and those with low clinical risk but high genomic risk) were randomly assigned (1:1) to receive chemotherapy or not based on either the clinical risk or the genomic risk. Randomisation was done centrally and used a minimisation technique that was stratified by institution, risk group, and clinical-pathological characteristics. Treatment allocation was not masked. The primary endpoint was to test whether the distant metastasis-free survival rate at 5 years in patients with high clinical risk and low genomic risk not receiving chemotherapy had a lower boundary of the 95% CI above the predefined non-inferiority boundary of 92%. In the primary test population of patients with high clinical risk and low genomic risk who adhered to the treatment allocation of no chemotherapy and had no change in risk post-enrolment. Here, we present updated follow-up as well as an exploratory analysis of a potential age effect (≤50 years vs >50 years) and an analysis by nodal status for patients with hormone receptor-positive and HER2-negative disease. These analyses were done in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT00433589, and the European Clinical Trials database, EudraCT2005-002625-31. Recruitment is complete and further long-term follow-up is ongoing. FINDINGS: Between Feb 8, 2007, and July 11, 2011, 6693 patients were enrolled. On Feb 26, 2020, median follow-up was 8·7 years (IQR 7·8-9·7). The updated 5-year distant metastasis-free survival rate for patients with high clinical risk and low genomic risk receiving no chemotherapy (primary test population, n=644) was 95·1% (95% CI 93·1-96·6), which is above the predefined non-inferiority boundary of 92%, supporting the previous analysis and proving MINDACT as a positive de-escalation trial. Patients with high clinical risk and low genomic risk were randomly assigned to receive chemotherapy (n=749) or not (n=748); this was the intention-to-treat population. The 8-year estimates for distant metastasis-free survival in the intention-to-treat population were 92·0% (95% CI 89·6-93·8) for chemotherapy versus 89·4% (86·8-91·5) for no chemotherapy (hazard ratio 0·66; 95% CI 0·48-0·92). An exploratory analysis confined to the subset of patients with hormone receptor-positive, HER2-negative disease (1358 [90.7%] of 1497 randomly assigned patients, of whom 676 received chemotherapy and 682 did not) shows different effects of chemotherapy administration on 8-year distant metastasis-free survival according to age: 93·6% (95% CI 89·3-96·3) with chemotherapy versus 88·6% (83·5-92·3) without chemotherapy in 464 women aged 50 years or younger (absolute difference 5·0 percentage points [SE 2·8, 95% CI -0·5 to 10·4]) and 90·2% (86·8-92·7) versus 90·0% (86·6-92·6) in 894 women older than 50 years (absolute difference 0·2 percentage points [2·1, -4·0 to 4·4]). The 8-year distant metastasis-free survival in the exploratory analysis by nodal status in these patients was 91·7% (95% CI 88·1-94·3) with chemotherapy and 89·2% (85·2-92·2) without chemotherapy in 699 node-negative patients (absolute difference 2·5 percentage points [SE 2·3, 95% CI -2·1 to 7·2]) and 91·2% (87·2-94·0) versus 89·9% (85·8-92·8) for 658 patients with one to three positive nodes (absolute difference 1·3 percentage points [2·4, -3·5 to 6·1]). INTERPRETATION: With a more mature follow-up approaching 9 years, the 70-gene signature shows an intact ability of identifying among women with high clinical risk, a subgroup, namely patients with a low genomic risk, with an excellent distant metastasis-free survival when treated with endocrine therapy alone. For these women the magnitude of the benefit from adding chemotherapy to endocrine therapy remains small (2·6 percentage points) and is not enhanced by nodal positivity. However, in an underpowered exploratory analysis this benefit appears to be age-dependent, as it is only seen in women younger than 50 years where it reaches a clinically relevant threshold of 5 percentage points. Although, possibly due to chemotherapy-induced ovarian function suppression, it should be part of informed, shared decision making. Further study is needed in younger women, who might need reinforced endocrine therapy to forego chemotherapy. FUNDING: European Commission Sixth Framework Programme.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Transcriptoma/genética , Adolescente , Adulto , Fatores Etários , Idoso , Antraciclinas/administração & dosagem , Neoplasias da Mama/patologia , Hidrocarbonetos Aromáticos com Pontes/administração & dosagem , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Taxoides/administração & dosagem , Resultado do Tratamento , Adulto Jovem
2.
Ann Hematol ; 100(4): 1013-1021, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33634349

RESUMO

The prognosis of elderly patients diagnosed with diffuse large B cell lymphoma (DLBCL) is considered to be clearly inferior to that of younger patients. Besides tumor biology and comorbidities, treatment selection due to an assumed reduced tolerability may contribute to this difference. With increasingly more patients diagnosed at advanced age, current treatment selections need to be reviewed carefully. Hence, we analyzed the results of patients above the age of 70 in whom a diagnosis of DLBCL was made. Whereas patients up to 80 were frequently selected for and were able to tolerate standard treatment (86% intended use, 74% completion), patients above the age of 80 years were not only treated more cautiously (67 and 60%, respectively) but did show inferior response to treatment with standard treatment (CR rate for intended R-CHOP use 64% vs. 43%). However, on an individual level, patients receiving and completing standard treatment obtained results that resemble the results of younger patients, irrespective if aged more than 80 and impose superior to prior reports in this age cohort. Median PFS for the entire group of patients was 3.44 years, with 4.83 years for patients below 80 and only 1.09 years for patients above the age of 80. The corresponding figures for OS were 7.38 years (estimated); after 2 years, OS was 81% in the younger cohort in contrast to 68% in patients > 80 years. However, for patients not planned to receive or not tolerating R-CHOP, results remain poor; tailored approaches for these patients are required.


Assuntos
Linfoma Difuso de Grandes Células B/epidemiologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Antraciclinas/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Combinada , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Humanos , Estimativa de Kaplan-Meier , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/radioterapia , Masculino , Prednisona/administração & dosagem , Prognóstico , Intervalo Livre de Progressão , Radioterapia Adjuvante , Rituximab/administração & dosagem , Resultado do Tratamento , Vincristina/administração & dosagem
3.
Anticancer Res ; 41(2): 1063-1068, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33517316

RESUMO

BACKGROUND/AIM: We evaluated the impact of the relative dose intensity (RDI) of neoadjuvant chemotherapy (NAC) on the survival of patients with breast cancer (BC). PATIENTS AND METHODS: This randomized phase II trial included 188 patients with human epidermal growth factor receptor 2 (HER2)-negative BC treated with anthracycline followed by paclitaxel as NAC. We grouped patients using a relative dose intensity (RDI) threshold of 85% and evaluated clinicopathological features and clinical outcomes. RESULTS: The 5-year overall survival rate was 91.2% and 76.3%, when RDI ≥85% and <85%, respectively (p=0.015). Age, tumor, and node status, and the RDI were significantly different on univariate analysis, but not on multivariate analysis. An exploratory subgroup analysis revealed that a low RDI was associated with low overall survival of patients with obesity, T1/2 disease, and lymph node metastases. CONCLUSION: Maintaining the RDI of NAC is crucial for achieving the survival benefit in selected patients with HER2-negative BC.


Assuntos
Antraciclinas/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Paclitaxel/administração & dosagem , Receptor ErbB-2/metabolismo , Adulto , Idoso , Antraciclinas/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Esquema de Medicação , Cálculos da Dosagem de Medicamento , Feminino , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante , Paclitaxel/uso terapêutico , Análise de Sobrevida , Resultado do Tratamento
4.
Oncology ; 98(9): 653-660, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32454480

RESUMO

BACKGROUND: Anthracycline is used to treat various types of cancer; however, cardiotoxicity negatively affects patient prognosis. OBJECTIVES: The aim of the present study was to investigate serial changes in levels of cardiac troponin I (TnI) and B-type natriuretic peptide (BNP) in patients treated with anthracycline-containing therapy. METHODS: 91 consecutive cancer patients planned for anthracycline treatment were enrolled and followed up for 12 months. All patients underwent echocardiography and blood sampling at baseline, 3, 6, and 12 months. RESULTS: The patients were divided into two groups based on their TnI level during the follow-up period: the elevated TnI group (TnI ≥0.03 ng/mL; n = 37) and the normal TnI group (n = 54). In the elevated TnI group, the TnI levels increased at 3 and 6 months, but they returned to within normal range at 12 months after anthracycline administration. Unlike TnI, the BNP levels began to increase after 6 months, and remained increased at 12 months. The occurrence of cancer therapeutics-related cardiac dysfunction was higher in the elevated TnI group than in the normal TnI group. When we set the cut-off value of TnI at 0.029 ng/mL, sensitivity and specificity to predict an elevated BNP level of more than 100 pg/mL were 90 and 63%, respectively. Multivariate logistic regression analysis revealed that elevated TnI was an independent predictor of elevated BNP levels. CONCLUSION: Elevated TnI was an independent predictor for the development of BNP increase. The different characteristics of TnI and BNP should be considered when managing patients treated with anthracycline-containing therapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Cardiotoxicidade/sangue , Peptídeo Natriurético Encefálico/sangue , Neoplasias/sangue , Neoplasias/tratamento farmacológico , Troponina I/sangue , Antraciclinas/administração & dosagem , Antraciclinas/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cardiotoxicidade/diagnóstico por imagem , Cardiotoxicidade/etiologia , Ecocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes
5.
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
6.
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
7.
Int J Oncol ; 56(3): 848-856, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32124968

RESUMO

Squamous cell lung carcinoma (SQCLC) is an aggressive type of lung cancer. In contrast with the marked advances that have been achieved in the treatment of lung adenocarcinoma, there are currently no effective targeted therapies for SQCLC, for with cytotoxic drugs are still the main treatment strategy. Therefore, the present study aimed to develop novel combination therapies for SQCLC. The results demonstrated that a combined treatment with the potent histone deacetylase (HDAC) inhibitor OBP­801 and the third­generation anthracycline amrubicin synergistically inhibited the viability of SQCLC cell lines by inducing apoptosis signal­regulating kinase 1 (ASK1)­dependent, as well as JNK­ and p38 mitogen­activated protein kinase (MAPK)­independent apoptosis. OBP­801 treatment strongly induced the protein expression levels of thioredoxin­interacting protein (TXNIP), and amrubicin treatment increased the levels of intracellular reactive oxygen species (ROS), which suggested that this combination oxidized and dissociated thioredoxin 2 (Trx2) from mitochondrial ASK1 and activated ASK1. Moreover, mouse xenograft experiments using human H520 SQCLC cells revealed that the co­treatment potently suppressed tumor growth in vivo. These results suggested that a combined treatment with OBP­801 and amrubicin may have potential as a therapeutic strategy for SQCLC.


Assuntos
Antraciclinas/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Inibidores de Histona Desacetilases/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , MAP Quinase Quinase Quinase 5/metabolismo , Peptídeos Cíclicos/administração & dosagem , Animais , Antraciclinas/farmacologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sinergismo Farmacológico , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Inibidores de Histona Desacetilases/farmacologia , Humanos , Neoplasias Pulmonares/metabolismo , Camundongos , Peptídeos Cíclicos/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
8.
Cancer Metastasis Rev ; 39(1): 55-68, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32026204

RESUMO

Over the past few decades, the diagnosis and management of children with various malignancies have improved tremendously. As a result, there are an increasing number of children who are long-term cancer survivors. With improved survival, however, has come an increased risk of treatment-related cardiovascular complications that can appear decades after treatment. These problems are serious enough that all caregivers of childhood cancer survivors, including oncologists, cardiologists, and other health care personnel, must pay close attention to the short- and long-term effects of chemotherapy and radiotherapy on these children. This review discusses the effects of treatment-related cardiovascular complications from anthracyclines and radiotherapy and the methods for preventing, screening, and treating these complications.


Assuntos
Sobreviventes de Câncer , Doenças Cardiovasculares/etiologia , Neoplasias/complicações , Antraciclinas/administração & dosagem , Antraciclinas/efeitos adversos , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Doenças Cardiovasculares/induzido quimicamente , Criança , Humanos , Neoplasias/terapia
11.
Sci Rep ; 10(1): 685, 2020 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-31959790

RESUMO

Repeated cycles of post-remission high-dose cytarabine (Ara-C) have been suggested to improve survival in core binding factor (CBF) acute myeloid leukaemia (AML). High-dose Ara-C used for induction regimens has also been reported to be associated with increased treatment-related mortality (TRM). Few data are available about intermediate-dose Ara-C serving as induction therapy. The aim of our study was to compare the tolerance and outcomes of standard- and intermediate-dose levels of Ara-C as induction in CBF AML and to analyse the clinical heterogeneity of the two AML entities under these induction settings. We retrospectively investigated the outcomes in adults with CBF AML induced with regimens based on standard-dose Ara-C at 100 to 200 mg/m2 or intermediate-dose Ara-C at 1,000 mg/m2. In total, 152 patients with t(8; 21) and 54 patients with inv(16) AML were administered an induction regimen containing anthracyclines plus either standard- or intermediate-dose Ara-C. After a single course of induction, the complete remission (CR) rate in the inv(16) cohort was 52/52 (100%), higher than the 127/147 (86.4%) in the t(8; 21) cohort (P = 0.005). Intermediate-dose Ara-C (HR = 9.931 [2.135-46.188], P = 0.003) and negative KITmut (HR = 0.304 [0.106-0.874], P = 0.027) independently produced an increased CR rate in the t(8; 21) cohort. Positive CD19 expression (HR = 0.133 [0.045-0.387], P = 0.000) and sex (male) (HR = 0.238 [0.085-0.667], P = 0.006) were associated with superior leukaemia-free survival (LFS) in the t(8; 21) cohort independently of KITmut status or the induction regimen. We conclude that intermediate-dose Ara-C is superior to standard-dose Ara-C for induction of remission in t(8; 21) AML, and CD19 status and sex independently confer prognostic significance for LFS. The KITmut status alone does not have an independent effect on survival in t(8; 21) AML. More intensive induction therapy is unnecessary in inv(16) AML.


Assuntos
Antraciclinas/administração & dosagem , Antimetabólitos Antineoplásicos/administração & dosagem , Inversão Cromossômica , Citarabina/administração & dosagem , Leucemia Mieloide Aguda/tratamento farmacológico , Translocação Genética , Adolescente , Adulto , Antraciclinas/efeitos adversos , Antimetabólitos Antineoplásicos/efeitos adversos , Citarabina/efeitos adversos , Esquema de Medicação , Cálculos da Dosagem de Medicamento , Feminino , Humanos , Quimioterapia de Indução , Leucemia Mieloide Aguda/genética , Masculino , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas c-kit/genética , Estudos Retrospectivos , Fatores Sexuais , Resultado do Tratamento , Adulto Jovem
12.
Breast Cancer Res Treat ; 179(3): 533-542, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31865475

RESUMO

PURPOSE: Triple-negative breast cancer (TNBC) pertains to a breast cancer subtype that has the highest metastatic and recurrence rates. The effectiveness of capecitabine as adjuvant chemotherapy for TNBC has remained unclear. This study conducted a meta-analysis of the efficacy of capecitabine as adjuvant chemotherapy for early-stage TNBC treated with taxane-/anthracycline-based chemotherapy. METHODS: We identified relevant research reports in online databases until May 2019. We finally included seven randomized clinical trials to perform this meta-analysis. Altogether, the seven trials enrolled 3151 early-stage TNBC patients, with 1552 receiving standard (neo)adjuvant chemotherapy regimens and 1599 receiving addition of capecitabine in the adjuvant settings besides standard regimens. RESULTS: A meta-analysis of the seven trials revealed a significant increase in disease-free survival (DFS) with the addition of capecitabine (Hazard ratio (HR) = 0.77, 95% CI 0.66-0.90). This improvement in DFS was significant both in trials conducted in America-Europe and in Asia. In trials involving six to eight cycles of capecitabine addition, we observed a significant improvement in DFS. Furthermore, in the meta-analysis of six trials, we detected a significant increase in overall survival (OS) favoring capecitabine (HR = 0.69, 95% CI 0.56-0.85). CONCLUSIONS: Adjuvant addition of capecitabine to early-stage TNBC patients receiving standard chemotherapy showed significant DFS and OS improvement. Future studies involving the selection of patients that may have the highest survival benefit from adding capecitabine are warranted.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia , Antraciclinas/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Hidrocarbonetos Aromáticos com Pontes/administração & dosagem , Capecitabina/administração & dosagem , Quimioterapia Adjuvante , Feminino , Humanos , Estadiamento de Neoplasias , Prognóstico , Retratamento , Taxoides/administração & dosagem , Resultado do Tratamento , Neoplasias de Mama Triplo Negativas/mortalidade
13.
Radiother Oncol ; 142: 52-61, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31785830

RESUMO

BACKGROUND: The optimal sequence of adjuvant chemotherapy and radiotherapy for breast cancer is unknown. SECRAB assesses whether local control can be improved without increased toxicity. METHODS: SECRAB was a prospective, open-label, multi-centre, phase III trial comparing synchronous to sequential chemo-radiotherapy, conducted in 48 UK centres. Patients with invasive, early stage breast cancer were eligible. Randomisation (performed using random permuted block assignment) was stratified by centre, axillary surgery, chemotherapy, and radiotherapy boost. Permitted chemotherapy regimens included CMF and anthracycline-CMF. Synchronous radiotherapy was administered between cycles two and three for CMF or five and six for anthracycline-CMF. Sequential radiotherapy was delivered on chemotherapy completion. Radiotherapy schedules included 40 Gy/15F over three weeks, and 50 Gy/25F over five weeks. The primary outcome was local recurrence at five and ten years, defined as time to local recurrence, and analysed by intention to treat. ClinicalTrials.gov NCT00003893. FINDINGS: Between 02-July-1998 and 25-March-2004, 2297 patients were recruited (1150 synchronous and 1146 sequential). Baseline characteristics were balanced. With 10.2 years median follow-up, the ten-year local recurrence rates were 4.6% and 7.1% in the synchronous and sequential arms respectively (hazard ratio (HR) 0.62; 95% confidence interval (CI): 0.43-0.90; p = 0.012). In a planned sub-group analysis of anthracycline-CMF, the ten-year local recurrence rates difference were 3.5% versus 6.7% respectively (HR 0.48 95% CI: 0.26-0.88; p = 0.018). There was no significant difference in overall or disease-free survival. 24% of patients on the synchronous arm suffered moderate/severe acute skin reactions compared to 15% on the sequential arm (p < 0.0001). There were no significant differences in late adverse effects apart from telangiectasia (p = 0.03). INTERPRETATION: Synchronous chemo-radiotherapy significantly improved local recurrence rates. This was delivered with an acceptable increase in acute toxicity. The greatest benefit of synchronous chemo-radiation was in patients treated with anthracycline-CMF. FUNDING: Cancer Research UK (CR UK/98/001) and Pharmacia.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/radioterapia , Adulto , Idoso , Antraciclinas/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/patologia , Quimiorradioterapia Adjuvante , Cisplatino/administração & dosagem , Intervalo Livre de Doença , Feminino , Fluoruracila/administração & dosagem , Humanos , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Estudos Prospectivos , Resultado do Tratamento , Adulto Jovem
14.
J Clin Oncol ; 38(1): 29-42, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31622133

RESUMO

PURPOSE: Exercise intolerance, associated with heart failure and death in general populations, is not well studied in survivors of childhood cancer. We examined prevalence of exercise intolerance in survivors exposed or not to cardiotoxic therapy, and associations among organ system function, exercise intolerance, and mortality. METHODS: Participants consisted of 1,041 people who had survived cancer ≥ 10 years (and had or did not have exposure to anthracyclines and/or chest-directed radiation) and 285 control subjects. Exercise intolerance was defined as peak oxygen uptake < 85% predicted from maximal cardiopulmonary exercise testing; organ functions were ascertained with imaging or clinical testing. Multivariable regression of the data was performed to compare exercise capacity between survivors exposed or unexposed to cardiotoxic therapy and control subjects, and to evaluate associations between treatment and organ function, and organ function and exercise intolerance. Propensity score methods in time-to-event analyses evaluated associations between exercise intolerance and mortality. RESULTS: Survivors (mean age ± standard deviation [SD], 35.6 ± 8.8 years) had lower mean (± SD) peak oxygen uptake (exposed: 25.74 ± 8.36 mL/kg/min; unexposed: 26.82 ± 8.36 mL/kg/min) than did control subjects (32.69 ± 7.75 mL/kg/min; P for all < .001). Exercise intolerance was present in 63.8% (95% CI, 62.0% to 65.8%) of exposed survivors, 55.7% (95% CI, 53.2% to 58.2%) of unexposed survivors, and 26.3% (95% CI, 24.0% to 28.3%) of control subjects, and was associated with mortality (hazard ratio, 3.9; 95% CI, 1.09 to 14.14). Global longitudinal strain (odds ratio [OR], 1.71; 95% CI, 1.11 to 2.63), chronotropic incompetence (OR, 3.58; 95% CI, 1.75 to 7.31); forced expiratory volume in 1 second < 80% (OR, 2.59; 95% CI, 1.65 to 4.09), and 1 SD decrease in quadriceps strength (OR, 1.49; 95% CI, 1.23 to 1.82) were associated with exercise intolerance. Ejection fraction < 53% was not associated with exercise intolerance. CONCLUSION: Exercise intolerance is prevalent among childhood cancer survivors and associated with all-cause mortality. Treatment-related cardiac (detected by global longitudinal strain), autonomic, pulmonary, and muscular impairments increased risk. Survivors with impairments may require referral to trained specialists to learn to accommodate specific deficits when engaging in exercise.


Assuntos
Sobreviventes de Câncer/estatística & dados numéricos , Tolerância ao Exercício/fisiologia , Insuficiência de Múltiplos Órgãos/mortalidade , Insuficiência de Múltiplos Órgãos/fisiopatologia , Neoplasias/mortalidade , Neoplasias/fisiopatologia , Adulto , Antraciclinas/administração & dosagem , Antraciclinas/efeitos adversos , Teste de Esforço , Feminino , Cardiopatias/epidemiologia , Cardiopatias/mortalidade , Cardiopatias/fisiopatologia , Humanos , Masculino , Insuficiência de Múltiplos Órgãos/epidemiologia , Neoplasias/tratamento farmacológico , Neoplasias/epidemiologia , Consumo de Oxigênio/fisiologia , Ensaios Clínicos Controlados Aleatórios como Assunto
15.
Cancer Chemother Pharmacol ; 85(3): 509-515, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31654111

RESUMO

PURPOSE: To evaluate the predictive value of the in vitro chemosensitivity using ATP-TCA method to compare the clinical efficacy of patients with AML. METHODS: Bone marrow or peripheral blood samples were collected from 65 patients with AML, and the in vitro chemosensitivity of four drugs (cytarabine/idarubicin/decitabine/aclacinomycin) was measured by an ATP-tumor chemosensitivity assay. RESULTS: Aclacinomycin and cytarabine had the highest chemosensitivity rates (66.7%, 8/12 and 58.5%, 38/65, respectively), while idarubicin and decitabine had rates of 6.5% (3/46) and 0% (0/35), respectively. Complete remission (CR) was achieved in 66.2% (43/65) of patients, and there was a statistically significant correlation between CR and in vitro chemosensitivity for cytarabine (47.7% vs 18.5%, p = 0.002), but not for the anthracyclines (p = 0.950). In addition, three other factors significantly correlated with CR: disease status (p = 0.005), FLT3-ITD/TKD mutation (p = 0.003) and chemotherapy regimens (p = 0.004). Furthermore, multiple logistic regression analysis revealed that the sensitivity of cytarabine was one of the significant risk factors for CR [hazard ratio (HR) = 5.52; 95% confidence interval (CI) = 1.47-20.70; p = 0.011]. CONCLUSIONS: The in vitro chemosensitivity as tested by ATP-TCA demonstrated a significant correlation with CR for chemotherapy and can be a useful tool to optimize personalized treatments for patients with AML.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Aclarubicina/análogos & derivados , Adulto , Antraciclinas/administração & dosagem , Citarabina/administração & dosagem , Decitabina/administração & dosagem , Feminino , Humanos , Idarubicina/administração & dosagem , Quimioterapia de Indução/métodos , Leucemia Mieloide Aguda/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Indução de Remissão/métodos , Estudos Retrospectivos , Adulto Jovem
16.
Int J Cardiol ; 299: 271-275, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-31422879

RESUMO

AIMS: Cardiovascular disease is a well-recognized cause of increased late morbidity and mortality among survivors of childhood cancer treated with anthracyclines. Co-administration of Dexrazoxane has been shown to significantly reduce short-term and mid-term cardiotoxicity. Aim of this study was to assess cardiac function in long-term (>10 years) survivors of childhood tumors treated with dexrazoxane/anthracycline association. METHODS AND RESULTS: Twenty cancer survivors previously treated with co-administration of anthracyclines-dexrazoxane for childhood renal tumors or sarcoma and a control group of 20 healthy subjects were enrolled in the study. Echocardiographic measurements included 3D left ventricular (LV) ejection fraction (LVEF) and LV and right ventricular (RV) global longitudinal strain (GLS). Among cancer survivors group the median age at diagnosis was 5 years (1-17) and they were evaluated at median follow-up time of 21.5 years (10-26). No evidence of cardiac toxicity, as defined by current guidelines, was reported in all survivors. No significant differences in standard and deformation imaging parameters were observed between survivors and controls (3D LVEF 58 ±â€¯3% vs 60 ±â€¯5% p = NS; LV GLS -21 ±â€¯1% vs -21 ±â€¯2% p = NS; RV GLS -23 ±â€¯2% vs -23 ±â€¯5% p = NS). No second tumor was registered in dexrazoxane-treated survivors. CONCLUSIONS: Our findings may support the role of dexrazoxane as a useful strategy for cardio-protection in children undergoing anthracycline based treatment. However, large randomized trials are needed to confirm the cardio-protective role of dexrazoxane in pediatric setting at long-term follow-up.


Assuntos
Antraciclinas/administração & dosagem , Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Sobreviventes de Câncer , Dexrazoxano/administração & dosagem , Ecocardiografia/tendências , Adulto , Ecocardiografia/efeitos dos fármacos , Feminino , Seguimentos , Humanos , Masculino , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
17.
J Oncol Pharm Pract ; 26(3): 572-579, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31256745

RESUMO

BACKGROUND: Pertuzumab-based neoadjuvant chemotherapy (NAC) has demonstrated successful pathologic complete response (pCR) rates when administered to patients with human epidermal growth factor receptor 2 (HER2)-positive, locally advanced breast cancer and has become standard of care. This study aimed to identify pCR rates in patients receiving a variety of pertuzumab-based NAC regimens. The effect of the addition of an anthracycline and impact of anthracycline and taxane sequencing on pCR was also assessed. METHODS: A retrospective, single-center review was conducted on patients with operable, human epidermal growth factor receptor 2 (HER2)-positive breast cancer that received one of five pertuzumab-containing NAC regimens followed by definitive surgery. RESULTS: Ninety-six patients were included in the analysis; overall, pCR was attained in 49 patients (51%). Of the 61 patients who received an anthracycline-containing NAC regimen, 30 (49%) attained a pCR. Of the 35 patients who received the non-anthracycline NAC regimen, 19 (54%) attained a pCR; difference in pCR was not statistically significant (p = 0.63). Anthracycline/taxane sequence analysis showed that of the patients attaining pCR with an anthracycline-containing NAC, 77% of patients received the taxane portion upfront (p = 0.17). Relative dose intensity of the anthracycline portion was similar irrespective of treatment sequence. However, relative dose intensity of the taxane portion was decreased with upfront anthracycline administration. CONCLUSION: These findings support current recommendations of adding pertuzumab to established regimens for treatment of locally advanced, HER2-positive, early stage breast cancer. The benefit of adding an anthracycline in the neoadjuvant setting remains unclear. Patients treated with the taxane portion of NAC upfront appeared to have a higher rate of pCR and better relative dose intensity than patients who received the anthracycline portion upfront, but differences were not statistically significant. These findings should be verified in a prospective clinical trial.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Adulto , Idoso , Antraciclinas/administração & dosagem , Anticorpos Monoclonais Humanizados/administração & dosagem , Hidrocarbonetos Aromáticos com Pontes/administração & dosagem , Feminino , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante , Receptor ErbB-2/metabolismo , Estudos Retrospectivos , Taxoides/administração & dosagem
18.
Cancer ; 126(1): 98-104, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31536651

RESUMO

BACKGROUND: Intimal sarcoma (InS) is an exceedingly rare neoplasm with an unfavorable prognosis, for which new potentially active treatments are under development. We report on the activity of anthracycline-based regimens, gemcitabine-based regimens, and pazopanib in patients with InS. METHODS: Seventeen sarcoma reference centers in Europe, the United States, and Japan contributed data to this retrospective analysis. Patients with MDM2-positive InS who were treated with anthracycline-based regimens, gemcitabine-based regimens, or pazopanib between October 2001 and January 2018 were selected. Local pathological review was performed to confirm diagnosis. Response was assessed by RECIST1.1. Recurrence-free survival (RFS), progression-free survival (PFS) and overall survival were computed by Kaplan-Meier method. RESULTS: Seventy-two patients were included (66 anthracycline-based regimens; 26 gemcitabine-based regimens; 12 pazopanib). In the anthracycline-based group, 24 (36%) patients were treated for localized disease, and 42 (64%) patients were treated for advanced disease. The real-world overall response rate (rwORR) was 38%. For patients with localized disease, the median RFS was 14.6 months. For patients with advanced disease, the median PFS was 7.7 months. No anthracycline-related cardiac toxicity was reported in patients with cardiac InS (n = 26). For gemcitabine and pazopanib, the rwORR was 8%, and the median PFS was 3.2 and 3.7 months, respectively. CONCLUSION: This retrospective series shows the activity of anthracycline-based regimens in InS. Of note, anthracyclines were used in patients with cardiac InS with no significant cardiac toxicity. The prognosis in patients with InS remains poor, and new active drugs and treatment strategies are needed.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Cardíacas/tratamento farmacológico , Sarcoma/tratamento farmacológico , Túnica Íntima/efeitos dos fármacos , Adulto , Idoso , Antraciclinas/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cardiotoxicidade , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Feminino , Neoplasias Cardíacas/genética , Neoplasias Cardíacas/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Intervalo Livre de Progressão , Proteínas Proto-Oncogênicas c-mdm2/genética , Pirimidinas/administração & dosagem , Sarcoma/genética , Sarcoma/patologia , Sulfonamidas/administração & dosagem , Resultado do Tratamento , Túnica Íntima/patologia
19.
Sci Rep ; 9(1): 16662, 2019 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-31723167

RESUMO

Several ongoing clinical trials are investigating the use of immuno-targeting therapy with programmed cell death protein-1 and programmed death-ligand 1 (PD-L1) inhibitors for triple-negative breast cancer. However, the role of PD-L1 expression in HER2-positive breast cancer remains unclear. We investigated the clinicopathological utility of PD-L1 expression in HER2-positive breast cancer. Cohort A included 248 patients with invasive breast cancer (all subtypes). Cohort B included 126 HER2-positive patients who received neoadjuvant chemotherapy (NAC) concomitant with trastuzumab. The relationship of PD-L1 expression on the cancer cells with clinicopathological factors including pathological complete response (pCR) and prognosis was investigated. In cohort A, 8.1% patients were PD-L1-positive; PD-L1 positivity showed a correlation with high degree of tumor-infiltrating lymphocytes (TILs), estrogen receptor negativity, progesterone receptor negativity, and high histological grade. In cohort B, 17.5% patients were PD-L1-positive; PD-L1 positivity showed a significant correlation with high degree of TILs and high abundance of CD8-positive TILs. The pCR rates were related to TILs and PD-L1 expression. Among PD-L1-negative patients, high CD8-positive TILs were associated with significantly better prognosis. In conclusion, 17.5% of HER2-positive type patients were PD-L1-positive. PD-L1 expression was associated with response to NAC with trastuzumab in patients with HER2-positive breast cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/patologia , Regulação Neoplásica da Expressão Gênica , Terapia Neoadjuvante/mortalidade , Antraciclinas/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Docetaxel/administração & dosagem , Feminino , Seguimentos , Humanos , Paclitaxel/administração & dosagem , Prognóstico , Receptor ErbB-2/metabolismo , Receptores Estrogênicos/metabolismo , Receptores de Progesterona/metabolismo , Taxa de Sobrevida , Trastuzumab/administração & dosagem
20.
Expert Rev Cardiovasc Ther ; 17(11): 791-799, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31715108

RESUMO

Introduction: Malignancies and cardiovascular disease are the two leading causes of mortality worldwide. There is a growing concern that anti-cancer drugs may lead to increased cardiovascular morbidity among cancer survivors. This may be the result of direct effects of the cancer treatment on heart function, or due to an indirect acceleration of atherosclerosis.Areas covered: We searched two bibliographic databases [PubMed, Scopus] and one full-text database (Google Scholar) for publications on chemotherapy and arterial stiffness since 1970. Anthracyclines, alkylating agents and tyrosine kinase inhibitors seem to affect arterial elastic properties. These effects can be non-reversible and may appear after treatment termination. Monoclonal antibodies may induce either a temporary increase or no change on arterial stiffness of patients with malignancies. Anti-microtubule agents and antimetabolites have not been extensively studied so far.Expert opinion: This literature review suggests that certain anticancer medications may impair arterial stiffness, and that assessment of arterial elastic properties before and after initiation of anti-neoplasmatic therapy may be clinically useful in order to develop protective strategies against chemotherapy-induced vascular effects. Further research is warranted to confirm the effects of anti-cancer agents on arterial stiffness, as well as their potential clinical implications. Future research lies in finding new targeted biomarkers identifying arterial stiffness such as micro RNAs while imaging techniques could also be implemented in assessment of vascular toxicity.


Assuntos
Antineoplásicos/efeitos adversos , Neoplasias/tratamento farmacológico , Rigidez Vascular/efeitos dos fármacos , Antraciclinas/administração & dosagem , Antraciclinas/efeitos adversos , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Antineoplásicos/administração & dosagem , Doenças Cardiovasculares/induzido quimicamente , Humanos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...