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1.
Lancet ; 388(10039): 73-85, 2016 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-26830752

RESUMO

Pancreatic cancer is a highly lethal disease, for which mortality closely parallels incidence. Most patients with pancreatic cancer remain asymptomatic until the disease reaches an advanced stage. There is no standard programme for screening patients at high risk of pancreatic cancer (eg, those with a family history of pancreatic cancer and chronic pancreatitis). Most pancreatic cancers arise from microscopic non-invasive epithelial proliferations within the pancreatic ducts, referred to as pancreatic intraepithelial neoplasias. There are four major driver genes for pancreatic cancer: KRAS, CDKN2A, TP53, and SMAD4. KRAS mutation and alterations in CDKN2A are early events in pancreatic tumorigenesis. Endoscopic ultrasonography and endoscopic ultrasonography-guided fine-needle aspiration offer high diagnostic ability for pancreatic cancer. Surgical resection is regarded as the only potentially curative treatment, and adjuvant chemotherapy with gemcitabine or S-1, an oral fluoropyrimidine derivative, is given after surgery. FOLFIRINOX (fluorouracil, folinic acid [leucovorin], irinotecan, and oxaliplatin) and gemcitabine plus nanoparticle albumin-bound paclitaxel (nab-paclitaxel) are the treatments of choice for patients who are not surgical candidates but have good performance status.


Assuntos
Carcinoma Ductal Pancreático/diagnóstico , Neoplasias Císticas, Mucinosas e Serosas/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Albuminas/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antígeno CA-19-9/metabolismo , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Antígeno Carcinoembrionário/metabolismo , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/terapia , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Endossonografia , Fluoruracila/administração & dosagem , Genes p16 , Humanos , Irinotecano , Leucovorina/administração & dosagem , Neoplasias Císticas, Mucinosas e Serosas/genética , Neoplasias Císticas, Mucinosas e Serosas/terapia , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Paclitaxel/administração & dosagem , Pancreatectomia , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/terapia , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteína Smad4/genética , Proteína Supressora de Tumor p53/genética , Gencitabina
2.
Int J Radiat Oncol Biol Phys ; 86(4): 678-85, 2013 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-23773391

RESUMO

PURPOSE: Long-term survival rates for patients with resected pancreatic ductal adenocarcinoma (PDAC) have stagnated at 20% for more than a decade, demonstrating the need to develop novel adjuvant therapies. Gemcitabine-erlotinib therapy has demonstrated a survival benefit for patients with metastatic PDAC. Here we report the first phase 2 study of erlotinib in combination with adjuvant chemoradiation and chemotherapy for resected PDAC. METHODS AND MATERIALS: Forty-eight patients with resected PDAC received adjuvant erlotinib (100 mg daily) and capecitabine (800 mg/m(2) twice daily Monday-Friday) concurrently with intensity modulated radiation therapy (IMRT), 50.4 Gy over 28 fractions followed by 4 cycles of gemcitabine (1000 mg/m(2) on days 1, 8, and 15 every 28 days) and erlotinib (100 mg daily). The primary endpoint was recurrence-free survival (RFS). RESULTS: The median follow-up time was 18.2 months (interquartile range, 13.8-27.1). Lymph nodes were positive in 85% of patients, and margins were positive in 17%. The median RFS was 15.6 months (95% confidence interval [CI], 13.4-17.9), and the median overall survival (OS) was 24.4 months (95% CI, 18.9-29.7). Multivariate analysis with adjustment for known prognostic factors showed that tumor diameter >3 cm was predictive for inferior RFS (hazard ratio, 4.01; P=.001) and OS (HR, 4.98; P=.02), and the development of dermatitis was associated with improved RFS (HR, 0.27; P=.009). During CRT and post-CRT chemotherapy, the rates of grade 3/4 toxicity were 31%/2% and 35%/8%, respectively. CONCLUSION: Erlotinib can be safely administered with adjuvant IMRT-based CRT and chemotherapy. The efficacy of this regimen appears comparable to that of existing adjuvant regimens. Radiation Therapy Oncology Group 0848 will ultimately determine whether erlotinib produces a survival benefit in patients with resected pancreatic cancer.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Ductal Pancreático/terapia , Quimiorradioterapia Adjuvante/métodos , Neoplasias Pancreáticas/terapia , Quinazolinas/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Capecitabina , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/patologia , Quimiorradioterapia Adjuvante/efeitos adversos , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Fracionamento da Dose de Radiação , Toxidermias/etiologia , Toxidermias/patologia , Cloridrato de Erlotinib , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/análogos & derivados , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Pancreatectomia , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Pancreaticoduodenectomia , Qualidade de Vida , Quinazolinas/administração & dosagem , Quinazolinas/efeitos adversos , Radioterapia de Intensidade Modulada , Gencitabina
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