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1.
N Engl J Med ; 385(5): 395-405, 2021 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-34320285

RESUMO

BACKGROUND: For postmenopausal women with hormone-receptor-positive breast cancer, the most effective duration for adjuvant therapy with an aromatase inhibitor remains unclear. METHODS: In this prospective, phase 3 trial, we randomly assigned postmenopausal women with hormone-receptor-positive breast cancer who had received 5 years of adjuvant endocrine therapy to receive the aromatase inhibitor anastrozole for an additional 2 years (2-year group, receiving a total of 7 years) or an additional 5 years (5-year group, receiving a total of 10 years). The primary end point was disease-free survival. The primary analysis included all the patients who were still participating in the trial and who had no recurrence 2 years after randomization (i.e., when treatment in the 2-year group had ended). Secondary end points were overall survival, contralateral breast cancer, second primary cancer, and clinical bone fracture. RESULTS: Among the 3484 women who were enrolled in the trial, 3208 remained in the trial without disease progression after the first 2 years of extended anastrozole treatment following randomization. Among these women, disease progression or death occurred in 335 women in each treatment group in the primary-analysis set at 8 years (hazard ratio, 0.99; 95% confidence interval [CI], 0.85 to 1.15; P = 0.90). No between-group differences occurred in most secondary end points, and subgroup analyses did not indicate differences in any particular subgroup. The risk of clinical bone fracture was higher in the 5-year group than in the 2-year group (hazard ratio, 1.35; 95% CI, 1.00 to 1.84). CONCLUSIONS: In postmenopausal women with hormone-receptor-positive breast cancer who had received 5 years of adjuvant endocrine therapy, extending hormone therapy by 5 years provided no benefit over a 2-year extension but was associated with a greater risk of bone fracture. (Funded by AstraZeneca and the Austrian Breast and Colorectal Cancer Study Group; ABCSG-16/SALSA ClinicalTrials.gov number, NCT00295620.).


Assuntos
Anastrozol/administração & dosagem , Inibidores da Aromatase/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Recidiva Local de Neoplasia/prevenção & controle , Administração Oral , Idoso , Anastrozol/efeitos adversos , Antineoplásicos Hormonais/administração & dosagem , Antineoplásicos Hormonais/uso terapêutico , Inibidores da Aromatase/efeitos adversos , Neoplasias da Mama/mortalidade , Neoplasias da Mama/cirurgia , Quimioterapia Adjuvante , Intervalo Livre de Doença , Fraturas Ósseas/epidemiologia , Fraturas Ósseas/etiologia , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Pós-Menopausa , Estudos Prospectivos , Receptores de Estrogênio , Receptores de Progesterona , Tamoxifeno/uso terapêutico
2.
Medicine (Baltimore) ; 99(19): e20149, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32384502

RESUMO

INTRODUCTION: Chemotherapy-induced peripheral neuropathy (CIPN) is a worldwide concern in patients receiving neurotoxic agents for cancer therapy. High tone external muscle stimulation is a promising therapeutic approach to alleviate symptoms of CIPN. METHODS: This pilot study aims to investigate whether the application of home-based high-tone external muscle stimulation therapy (HTEMS) improves symptoms of CIPN. The trial is planned as a therapist- and assessor-blinded, 1:1 randomized controlled study. A total of 50 patients with chemotherapy-induced peripheral polyneuropathy will be included. All patients will perform therapy at home. Study participants will be allocated randomly to the HTEMS therapy (intervention group) or to the transcutaneous electrical nerve stimulation (TENS, control group), respectively, following a standardized therapy schedule. Compliance of participants can be verified by reading out the tool box. Outcomes will be evaluated at baseline and after 8 weeks of home-based therapy. The primary outcome includes improvement of CIPN according to the patient-reported EORTC QLQ-CIPN 20 questionnaire. Secondary outcomes are the patient-reported change in health-related quality of life and clinician-reported changes of vibration sensibility, tendon reflexes, temperature sensibility, perception of touch, and strength of the lower leg muscles. Further a safety- and process evaluation will be performed. DISCUSSION: This pilot RCT aims to evaluate the impact of home-based HTEMS as compared to TENS in CIPN. There is a need for an effective treatment for CIPN and the results of this study are expected to possibly identify a novel and effective treatment strategy in the future.


Assuntos
Antineoplásicos/efeitos adversos , Polineuropatias/induzido quimicamente , Polineuropatias/terapia , Autocuidado/métodos , Estimulação Elétrica Nervosa Transcutânea/métodos , Adolescente , Adulto , Fatores Etários , Idoso , Pesos e Medidas Corporais , Fumar Cigarros/epidemiologia , Método Duplo-Cego , Escolaridade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Força Muscular , Cooperação do Paciente , Projetos Piloto , Qualidade de Vida , Reflexo de Estiramento , Projetos de Pesquisa , Índice de Gravidade de Doença , Fatores Sexuais , Sensação Térmica , Tato , Adulto Jovem
3.
Nat Commun ; 9(1): 1219, 2018 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-29572535

RESUMO

Assessing the phenotypic diversity underlying tumour progression requires the identification of variations in the respective molecular interaction networks. Here we report proof-of-concept for a platform called poly-ligand profiling (PLP) that surveys these system states and distinguishes breast cancer patients who did or did not derive benefit from trastuzumab. We perform tissue-SELEX on breast cancer specimens to enrich single-stranded DNA (ssDNA) libraries that preferentially interact with molecular components associated with the two clinical phenotypes. Testing of independent sample sets verifies the ability of PLP to classify trastuzumab-treated patients according to their clinical outcomes with ROC-AUC of 0.78. Standard HER2 testing of the same patients gives a ROC-AUC of 0.47. Kaplan-Meier analysis reveals a median increase in benefit from trastuzumab-containing treatments of 300 days for PLP-positive compared to PLP-negative patients. If prospectively validated, PLP may increase success rates in precision oncology and clinical trials, thus improving both patient care and drug development.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Trastuzumab/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Área Sob a Curva , Biomarcadores Tumorais/análise , Neoplasias da Mama/genética , DNA de Cadeia Simples/análise , Progressão da Doença , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Ligantes , Pessoa de Meia-Idade , Fenótipo , Medicina de Precisão , Técnica de Seleção de Aptâmeros , Análise de Sequência de DNA , Resultado do Tratamento
4.
Breast Care (Basel) ; 9(5): 323-30, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25759612

RESUMO

Bone-targeted therapies like bisphosphonates (zoledronic acid or pamidronate) or denosumab are recommended in all patients with metastatic breast cancer and bone metastases, whether they are symptomatic or not. The choice between these 2 different agents, however, remains open. In this review, we critically discuss the emerging evidence for direct anti-tumor activity of bone-targeting agents, the utility of bone turnover markers for treatment decision and efficacy prediction, as well as the safety and financial aspects of bisphosphonates and denosumab. Furthermore, we provide a possible therapeutic algorithm, and present new pharmacologic agents which are being investigated for the treatment of metastatic bone disease.

5.
J Oncol ; 2013: 732047, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24027583

RESUMO

Traditionally, neoadjuvant treatment for breast cancer was preserved for locally advanced and inflammatory disease, converting an inoperable to a surgical resectable cancer. In recent years, neoadjuvant therapy has become an accepted treatment option also for lower tumor stages in order to increase the rate of breast conserving therapy and to reduce the extent of surgery. Furthermore, treatment response can be monitored, and therefore, patient compliance may be increased. Neoadjuvant trials, additionally, offer the opportunity to evaluate new treatment options in a faster way and with fewer patients than large adjuvant trials. Compared to the metastatic setting, the issue of acquired resistance and pretreatments, which may distort treatment efficacy, can be avoided. New trial designs like window-of-opportunity trials or postneoadjuvant trials provide the chance to identify tumor sensitivity or to overcome tumor resistance in early tumor stages. In particular, in HER2-positive breast cancer, the neoadjuvant approach yielded great successes. The dual HER2 blockade with trastuzumab and pertuzumab recently showed the highest pCR rates ever reported. Many new drugs are in clinical testing with the aim to further increase pCR rates. Whether this endpoint really represents a surrogate for long-term outcome is not answered yet and will be discussed in this review.

6.
Breast Care (Basel) ; 5(3): 158-162, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-21048830

RESUMO

BACKGROUND: The oral formulation of vinorelbine together with capecitabine allows for an all-oral combination chemotherapy which promises to raise quality of life of patients with advanced breast cancer. PATIENTS AND METHODS: Patients with HER2-negative, locally advanced, inoperable or metastatic breast cancer were included in this prospective observational trial (treatment schedule: capecitabine 500 mg/m2 twice daily, days 1-14; vinorelbine 60 mg/m2, days 1+8; repeated in 3-week cycles). RESULTS: All 32 patients (median age 50 years) were evaluable for toxicity, and 30 patients for response. Twentyfour patients received therapy as first-line treatment, and 8 patients as beyond first-line treatment. Median time to progression was 8 months, and median overall survival was 32 months. Complete response was observed in 1 patient (3%), partial response in 10 patients (33%), and disease stabilization for more than 6 months (SD > 6) in 10 patients (33%). This results in an overall response rate (ORR) of 37% and a clinical benefit rate (ORR + SD > 6) of 70%. The only grade 3/4 toxicities were neutropenia (19%) and hand-foot syndrome (9%). CONCLUSIONS: The all-oral combination of capecitabine/vinorelbine at this schedule appears to be an effective, well-tolerated regimen for treatment of advanced breast cancer, and offers a promising alternative to single-agent capecitabine and vinorelbine as well as intravenous polychemotherapy.

7.
BMC Cancer ; 9: 367, 2009 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-19835621

RESUMO

BACKGROUND: In Her2-positive advanced breast cancer, the upfront use of trastuzumab is well established. Upon progression on first-line therapy, patients may be switched to lapatinib. Others however remain candidates for continued antibody treatment (treatment beyond progression). Here, we aimed to identify factors predicting for activity of second-line trastuzumab-based therapy. METHODS: Ninety-seven patients treated with > 1 line of trastuzumab-containing therapy were available for this analysis. Her2-status was determined by immunohistochemistry and re-analyzed by FISH if a score of 2+ was gained. Time to progression (TTP) on second-line therapy was defined as primary study endpoint. TTP and overall survival (OS) were estimated using the Kaplan-Meier product limit method. Multivariate analyses (Cox proportional hazards model, multinomial logistic regression) were applied in order to identify factors associated with TTP, response, OS, and incidence of brain metastases. p values < 0.05 were considered to indicate statistical significance. RESULTS: Median TTP on second-line trastuzumab-based therapy was 7 months (95% CI 5.74-8.26), and 8 months (95% CI 6.25-9.74) on first-line, respectively (n.s.). In the multivariate models, none of the clinical or histopthological features could reliably predict for activity of second-line trastuzumab-based treatment. OS was 43 months suggesting improved survival in patients treated with trastuzumab in multiple-lines. A significant deterioration of cardiac function was observed in three patients; 40.2% developed brain metastases while on second-line trastuzumab or thereafter. CONCLUSION: Trastuzumab beyond progression showed considerable activity. None of the variables investigated correlated with activity of second-line therapy. In order to predict for activity of second-line trastuzumab, it appears necessary to evaluate factors known to confer trastuzumab-resistance.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Antineoplásicos/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Receptor ErbB-2/metabolismo , Adulto , Idoso , Anticorpos Monoclonais Humanizados , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Receptor ErbB-2/genética , Estudos Retrospectivos , Trastuzumab
8.
Cancer Chemother Pharmacol ; 62(5): 903-10, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18256835

RESUMO

PURPOSE: In Her2-postive metastatic breast carcinoma, first-line trastuzumab-based therapy is well established; many centres continue antibody treatment beyond disease progression. In this trial, we evaluated the efficacy and safety of gemcitabine and trastuzumab after earlier exposure to anthracyclines, docetaxel and/or vinorelbine, and trastuzumab. METHODS: Twenty-nine consecutive patients were included as eligible. Patients received gemcitabine at a dose of 1,250 mg/m2 on day one and eight, every 21 days. Trastuzumab was administered in three-week cycles. Clinical benefit rate (CBR; CR + PR + SD > or = 6 months) was defined as primary endpoint. RESULTS: As of July 2007, all patients are evaluable for toxicity, and 26 for response. Earlier therapies consisted of trastuzumab (100%), anthracyclines (100%), vinorelbine (96.6%), docetaxel (72.4%), and capecitabine (72.4%). 19.2% of patients experienced PR, and SD > or = 6 months was observed in a further 26.9%, resulting in a CBR of 46.2%. Time to progression was median 3 months, and overall survival 17 months. Neutropenia (20.7%), thrombocytopenia (13.8%), and nausea (3.4%) were the only treatment-related adverse events that occurred with grade 3 or 4 intensity. Four patients (13.8%) developed brain metastases while on therapy. CONCLUSIONS: While CBR was low when compared to trastuzumab-based first-line therapy, it is higher than what would be expected from gemcitabine monotherapy in a similar setting. Together with the favourable toxicity profile, this regimen appears to be a safe and potentially effective salvage therapy option in a heavily pre-treated population.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Terapia de Salvação , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Humanizados , Antimetabólitos Antineoplásicos/administração & dosagem , Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/patologia , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Progressão da Doença , Feminino , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Trastuzumab , Falha de Tratamento
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