Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 4 de 4
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
J Clin Oncol ; 29(12): 1578-86, 2011 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-21422418

RESUMO

PURPOSE: Validated biomarkers predictive of response/resistance to anthracyclines in breast cancer are currently lacking. The neoadjuvant Trial of Principle (TOP) study, in which patients with estrogen receptor (ER) -negative tumors were treated with anthracycline (epirubicin) monotherapy, was specifically designed to evaluate the predictive value of topoisomerase II-α (TOP2A) and develop a gene expression signature to identify those patients who do not benefit from anthracyclines. PATIENTS AND METHODS: The TOP trial included 149 patients, 139 of whom were evaluable for response prediction analyses. The primary end point was pathologic complete response (pCR). TOP2A and gene expression profiles were evaluated using pre-epirubicin biopsies. Gene expression data from ER-negative samples of the EORTC (European Organisation for Research and Treatment of Cancer) 10994/BIG (Breast International Group) 00-01 and MDACC (MD Anderson Cancer Center) 2003-0321 neoadjuvant trials were used for validation purposes. RESULTS: A pCR was obtained in 14% of the evaluable patients in the TOP trial. TOP2A amplification, but not protein overexpression, was significantly associated with pCR (P ≤ .001 v P ≤ .33). We developed an anthracycline-based score (A-Score) combining three signatures: a TOP2A gene signature and two previously published signatures related to tumor invasion and immune response. The A-Score was characterized by a high negative predictive value ([NPV]; NPV, 0.98; 95% CI, 0.90 to 1.00) overall and in the human epidermal growth factor receptor 2 (HER2) -negative and HER2-positive subpopulations. Its performance was independently confirmed in the anthracycline-based arms of the two validation trials (BIG 00-01: NPV, 0.83; 95% CI, 0.64 to 0.94 and MDACC 2003-0321: NPV, 1.00; 95% CI, 0.80 to 1.00). CONCLUSION: Given its high NPV, the A-Score could become, if further validated, a useful clinical tool to identify those patients who do not benefit from anthracyclines and could therefore be spared the non-negligible adverse effects.


Assuntos
Antibióticos Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos , Epirubicina/uso terapêutico , Antibióticos Antineoplásicos/efeitos adversos , Antígenos de Neoplasias/análise , Antígenos de Neoplasias/genética , Biomarcadores Tumorais/análise , Biópsia , Neoplasias da Mama/enzimologia , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Quimioterapia Adjuvante , DNA Topoisomerases Tipo II/análise , DNA Topoisomerases Tipo II/genética , Proteínas de Ligação a DNA/análise , Proteínas de Ligação a DNA/antagonistas & inibidores , Proteínas de Ligação a DNA/genética , Resistencia a Medicamentos Antineoplásicos/genética , Epirubicina/efeitos adversos , Europa (Continente) , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante , Razão de Chances , Seleção de Pacientes , Proteínas de Ligação a Poli-ADP-Ribose , Valor Preditivo dos Testes , Estudos Prospectivos , Receptor ErbB-2/análise , Receptores de Estrogênio/análise , Reprodutibilidade dos Testes , Medição de Risco , Fatores de Risco , Texas , Falha de Tratamento
2.
Arch Gynecol Obstet ; 278(5): 457-62, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18273626

RESUMO

OBJECTIVES: The prognosis of patients with platinum refractory disease is dismal. We present data from heavily pretreated patients to whom the folinic acid, 5-fluorouracil and oxaliplatin (Folfox) regimen was administered. The objectives were to assess response rate and to evaluate the safety profile. METHODS: Patients with recurrent, resistant or refractory pretreated ovarian carcinoma were eligible for oxaliplatin (85 mg/m(2)) and leucovorin (200 mg/m(2)), both given as a 2-h infusion on day 1, followed by a 48-h infusion of 5FU 2,600 mg/m(2) every 2 weeks. RESULTS: Fourteen patients were treated. Median age: 56 years (49-70). Median number of previous chemotherapy regimens: 5 (3-10) and previous platinum-based regimens: 2 (1-3). Median chemotherapy-free interval (interval since the completion of the last-line chemotherapy before the administration of the Folfox regimen): 9.5 weeks (1-39). Median number of administered cycles of Folfox/patient: 8 (2-11 cycles). Two (14.5%) patients had a disease complete response, 2 (14.5%)-partial response, 4 (29%)-stable disease and 6 (43%)-progressive disease. Four (29%) patients had a CA-125 complete response, 2 (14.5%)-CA-125 partial response, 5 (35.5%)-stable CA-125 levels and 3 (21%)-progressive CA-125 levels. There were no grade 4 adverse events or deaths due to the treatment. No dose modifications were required due to toxicity. CONCLUSIONS: Folfox seems to be a valuable option for heavily pre-treated patients with ovarian cancer, with an overall response rate, according to RECIST criteria, of 29% and disease stabilization in an additional 29% of patients, with a manageable toxicity profile. These results support further assessment of Folfox as salvage treatment for patients with carcinoma of the ovary or fallopian tube.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma/tratamento farmacológico , Neoplasias das Tubas Uterinas/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Idoso , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma/patologia , Estudos de Coortes , Intervalo Livre de Doença , Neoplasias das Tubas Uterinas/patologia , Feminino , Fluoruracila/efeitos adversos , Humanos , Leucovorina/efeitos adversos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Neoplasias Ovarianas/patologia , Oxaliplatina , Resultado do Tratamento
3.
Breast Cancer Res Treat ; 109(1): 59-65, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-17592772

RESUMO

Fulvestrant (Faslodex) is a new estrogen receptor (ER) antagonist with no agonist effects that is licensed for the treatment of postmenopausal women with hormone-sensitive advanced breast cancer (ABC) who have progressed/recurred on prior antiestrogen therapy. The Faslodex Compassionate Use Program (CUP) provides expanded access to fulvestrant in countries where it is not yet available for patients who are not eligible to enter clinical trials. This analysis pools data from 402 patients who received fulvestrant as part of the CUP in Belgium, predominantly as 3rd- to 5th-line endocrine therapy for ABC. Two patients experienced partial responses and 118 experienced stable disease lasting>or=6 months, resulting in an overall clinical benefit rate of 29.9%. Fulvestrant was active in patients with multiple sites of metastases, visceral metastases, human epidermal growth factor receptor 2-positive disease and after heavy endocrine pre-treatment. Fulvestrant was well tolerated, with only six patients (1.5%) discontinuing treatment following adverse events. These data support the findings of previous CUP analyses and Phase II and III trials, suggesting that fulvestrant is a valuable addition to the treatment sequence for postmenopausal women with ABC who have progressed/recurred on prior endocrine therapy.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Estradiol/análogos & derivados , Adulto , Idoso , Idoso de 80 Anos ou mais , Bélgica , Sistema Endócrino , Estradiol/uso terapêutico , Estrogênios/metabolismo , Feminino , Fulvestranto , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Resultado do Tratamento
4.
Clin Cancer Res ; 8(1): 95-102, 2002 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11801544

RESUMO

Preclinical studies suggest that amifostine could protect against toxicities induced by taxoids. We conducted a clinical and pharmacokinetic pilot study to assess the feasibility and toxicity of the docetaxel plus amifostine combination and the absence of influence of amifostine on docetaxel pharmacokinetics. We included 18 previously treated women with metastatic breast cancer (median age, 58.5 years; range, 34-74) in this single-center study. They were to receive a first course of docetaxel at 100 mg/m(2) i.v. as a 1-h infusion, then subsequent courses of docetaxel at 100 mg/m(2) preceded by amifostine at 910 mg/m(2) given as a 15-min i.v. infusion. Treatment was given every 3 weeks until disease progression or occurrence of unacceptable toxicity. We focused on neutrophils nadir (NN), time to nadir occurrence, and time to recovery of a neutrophil count >2 x 10(9)/liter, means of which were compared between cycle 1 and each of the other cycles by paired Student's t test. The total number of administered cycles was 84 (median number/patient, 4; range, 1-8). One patient received only the first course of docetaxel and was therefore not evaluable for amifostine effect. Neutropenia grade >2 occurred in 16 patients and was febrile in only 1. Other hematological and nonhematological toxicities were mild and manageable. Amifostine had no obvious influence on docetaxel-induced myelotoxicity as expressed by NN, time to nadir occurrence, and time to recovery. The mean NN (1 x 10(6)/liter) was 345 (18 patients) for cycle 1, then 318 (17 patients), 330 (13 patients), 340 (11 patients), 470 (8 patients), 200 (8 patients), 680 (5 patients), and 545 (4 patients) for cycles 2, 3, 4, 5, 6, 7, and 8, respectively (P >0.2). Individual pharmacokinetic (PK) parameters of docetaxel estimated in 11 patients undergoing blood sampling showed no influence of amifostine on the PK profile of docetaxel. Mean clearances (liter/h/m(2)) and peak concentration (C(peak); ng/ml) were 29.9 at cycle 1 versus 32.8 at cycle 2 (not significant) and 2849.9 at cycle 1 versus 2542.5 at cycle 2 (not significant), respectively. The population analysis including those 11 patients and 49 additional patients receiving docetaxel in other studies confirmed those findings. This study does not support evidence for amifostine cytoprotection against docetaxel-induced myelosuppression and shows that there is no major influence of amifostine on docetaxel PK parameters. For the other toxicities, which are usually cumulative, the present study has design limitations and further comparative trials are warranted.


Assuntos
Amifostina/uso terapêutico , Antineoplásicos Fitogênicos/farmacocinética , Neoplasias da Mama/metabolismo , Paclitaxel/análogos & derivados , Paclitaxel/farmacocinética , Taxoides , Adulto , Idoso , Antineoplásicos Fitogênicos/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Docetaxel , Quimioterapia Combinada , Feminino , Humanos , Pessoa de Meia-Idade , Neutrófilos/metabolismo , Paclitaxel/efeitos adversos , Projetos Piloto , Taxa de Sobrevida , Vômito/induzido quimicamente
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...