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1.
Oncologist ; 15(9): 1016-22, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20798191

RESUMO

PURPOSE: Rash occurs in >50% of patients prescribed epidermal growth factor receptor (EGFR) inhibitors. This study was undertaken to determine whether sunscreen prevents or mitigates these rashes. METHODS: This placebo-controlled, double-blinded trial enrolled rash-free patients starting an EGFR inhibitor. Patients were randomly assigned to sunscreen with a sun protection factor of 60 applied twice a day for 28 days versus placebo. They were then monitored for rash and quality of life (Skindex-16) during the 4-week intervention and for an additional 4 weeks. RESULTS: Fifty-four patients received sunscreen, and 56 received placebo; the arms were balanced at baseline. During the 4-week intervention, physician-reported rash occurred in 38 (78%) and 39 (80%) sunscreen-treated and placebo-exposed patients, respectively (p = 1.00); no significant differences in rash rates emerged over the additional 4 weeks. There were no significant differences in rash severity, and patient-reported outcomes of rash yielded similar conclusions. Adjustment for sun intensity by geographical zone, season, and use of photosensitivity medications did not yield a significant difference in rash across study arms (p = .20). Quality of life scores declined but remained comparable between arms. CONCLUSIONS: Sunscreen, as prescribed in this trial, did not prevent or attenuate EGFR inhibitor-induced rash.


Assuntos
Anticorpos Monoclonais/efeitos adversos , Receptores ErbB/antagonistas & inibidores , Exantema/prevenção & controle , Neoplasias/tratamento farmacológico , Quinazolinas/efeitos adversos , Protetores Solares/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados , Cetuximab , Método Duplo-Cego , Cloridrato de Erlotinib , Exantema/induzido quimicamente , Feminino , Humanos , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Neoplasias/psicologia , Qualidade de Vida , Protetores Solares/efeitos adversos
2.
Clin Breast Cancer ; 6(5): 425-32, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16381626

RESUMO

PURPOSE: The efficacy and tolerability of 2 different schedules of paclitaxel/carboplatin/trastuzumab for HER2-overexpressing metastatic breast cancer (MBC) were evaluated in this parallel multicenter phase II trial. PATIENTS AND METHODS: Patients received every-3-week therapy (n = 43) consisting of a 200 mg/m(2) dose of paclitaxel/carboplatin area under the curve (AUC) of 6 mg/mL per minute and trastuzumab (an initial 8 mg/kg dose and subsequent 6 mg/kg doses) administered every 21 days for 8 cycles or weekly therapy (n = 48) consisting of an 80-mg/m(2) dose of paclitaxel/carboplatin AUC of 2 mg/mL per minute for 3 of 4 weeks, with weekly trastuzumab (an initial 4-mg/kg dose and subsequent 2-mg/kg doses) administered every 4 weeks for 6 cycles. Trastuzumab was continued until disease progression or unacceptable toxicity. HER2 status was confirmed by a central laboratory review. RESULTS: The overall response rate (ORR) with every-3-week therapy was 65% (90% confidence interval [CI], 51%-77%), with a median time to disease progression of 9.9 months and median overall survival (OS) time of 2.3 years. The ORR with weekly therapy was 81% (90% CI, 70%-90%), with a median time to disease progression of 13.8 months and a median OS time of 3.2 years. Hematologic and nonhematologic toxicities occurred significantly less frequently with weekly therapy versus every-3-week therapy: grade 3/4 neutropenia (52% vs. 88%); grade 3 thrombocytopenia (4% vs. 30%); and grade 3 neurosensory toxicity (2% vs. 19%), respectively. CONCLUSIONS: Every-3-week and weekly regimens of paclitaxel/carboplatin/trastuzumab are highly active in women with HER2-overexpressing MBC. However, fewer patients developed severe neutropenia, leukopenia, or thrombocytopenia with the weekly schedule.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Receptor ErbB-2/metabolismo , Adulto , Idoso , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Esquema de Medicação , Feminino , Humanos , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Taxa de Sobrevida , Trastuzumab , Resultado do Tratamento
3.
Exp Mol Pathol ; 72(3): 196-206, 2002 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12009783

RESUMO

The viral US3 and US6 gene products of human cytomegalovirus (CMV) are sequentially expressed at immediate-early and early times after infection, respectively. They downregulate the surface expression of HLA class I molecules. There are two repeat-containing regulatory regions between the US3 promoter and the US6 transcription unit designated R1 and R2. R2 contains repetitions of the NF-kappa B responsive element and enhances the immediate-early expression of the US3 gene. R1 contains 19 repetitions of a 5'-TRTCG-3' pentanucleotide arranged as everted repeats, inverted repeats, and variably spaced single pentanucleotides. In the context of the viral genome, R1 also enhances immediate-early US3 gene expression by an unknown mechanism (G. C. Bullock, et al., 2001, Virology 288, 164-174). We report a sequence motif within the R1 element that binds a human cell nuclear protein which is antigenically related to the Drosophila boundary element-associated factor (BEAF). The potential role of a 35-kDa cellular protein that binds to sequence motifs within the R1 element in regulating the expression of the CMV US3 immune evasion gene is discussed.


Assuntos
Citomegalovirus/genética , Citomegalovirus/imunologia , Genes Virais , Animais , Sequência de Bases , Sítios de Ligação/genética , Células Cultivadas , Citomegalovirus/metabolismo , DNA Viral/genética , DNA Viral/metabolismo , Proteínas de Ligação a DNA/metabolismo , Regulação Viral da Expressão Gênica , Genes Precoces , Glicoproteínas , Células HeLa , Humanos , Proteínas Imediatamente Precoces/genética , Proteínas de Membrana , Proteínas Nucleares/metabolismo , Ligação Proteica , Proteínas de Ligação a RNA/genética , Proteínas Virais/genética
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