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1.
Jpn J Clin Oncol ; 45(10): 953-62, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26206897

RESUMO

OBJECTIVE: Real-life safety and efficacy of sorafenib in advanced renal cell carcinoma in a nationwide patient population were evaluated by post-marketing all-patient surveillance. METHODS: All patients with unresectable or metastatic renal cell carcinoma in Japan who started sorafenib therapy from February 2008 to September 2009 were registered and followed for up to 12 months. Baseline characteristics, treatment status, tumor response, survival and safety data were recorded by the prescribing physicians. RESULTS: Safety and efficacy were evaluated in 3255 and 3171 patients, respectively. The initial daily dose was 800 mg in 78.2% of patients. Median duration of treatment was 6.7 months and the mean relative dose intensity was 68.4%. Overall, 2227 patients (68.4%) discontinued the treatment by 12 months, half of which (52.0% of discontinued patients) were due to adverse events. The most common adverse drug reactions were hand-foot skin reaction (59%), hypertension (36%), rash (25%) and increase in lipase/amylase (23%). The median progression-free survival was 7.3 months (95% confidence intervals: 6.7-8.1), and the overall survival rate at 1 year was 75.4% (73.5-77.1). Prognostic factors for overall survival were mostly consistent with those in previous clinical trials in the univariate analysis and largely similar to those for progression-free survival and duration of treatment in the multivariate analysis. CONCLUSIONS: Sorafenib for the treatment of advanced renal cell carcinoma under the labeled dose was feasible in daily medical practice, for its acceptable toxicity profile and favorable clinical benefit that were consistent with those in clinical trials.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Niacinamida/análogos & derivados , Compostos de Fenilureia/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Adulto , Idoso , Antineoplásicos/efeitos adversos , Carcinoma de Células Renais/secundário , Intervalo Livre de Doença , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Humanos , Japão , Neoplasias Renais/secundário , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Niacinamida/efeitos adversos , Niacinamida/uso terapêutico , Compostos de Fenilureia/efeitos adversos , Estudos Prospectivos , Inibidores de Proteínas Quinases/efeitos adversos , Sorafenibe , Análise de Sobrevida , Resultado do Tratamento
2.
Arch Dermatol Res ; 295(5): 183-9, 2003 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12883826

RESUMO

Staphylococcal superantigens (SsAgs) have gained attention as one of the factors aggravating atopic dermatitis (AD) and several potential mechanisms of AD aggravation by SsAgs have been reported. Tea catechin has been found to have many unique antimicrobiological activities such as antibacterial, antiviral, antifungal and antitoxic effects. In the present study, we investigated the inhibitory effect of the green tea catechin extract, Polyphenon, and (-)-epigallocatechin gallate (EGCg) on staphylococcal enterotoxin B (SEB) and its mechanisms of action, and we also discuss the possibility of therapeutic benefits for AD patients of tea catechin. Polyphenon inhibited the lethal toxicity of SEB and the SEB-induced production of TNF-alpha, IFN-gamma and IL-4 following its intraperitoneal administration to BALB/c mice. Although Polyphenon is composed of several isomers among which EGCg is approximately 50% of the total, we considered that most of the inhibitory effect of Polyphenon in mice could be attributed to EGCg. EGCg was immediately bound to SEB molecules and neutralized SEB in a dose- and incubation time-dependent manner without molecular weight alteration of the SEB molecule. Furthermore, EGCg inhibited SEB-induced TNF-alpha and IFN- gamma production and IL-2, IFN-gamma, IL-10 and IL-12 p40 mRNA expression in human PBMCs from normal donors in a dose-dependent manner. Inhibition of SsAg-induced T-cell activation by catechin was observed in both in vivo and in vitro studies, suggesting that catechin may be useful in the treatment of AD.


Assuntos
Antioxidantes/farmacologia , Catequina/análogos & derivados , Catequina/farmacologia , Dermatite Atópica/tratamento farmacológico , Enterotoxinas/toxicidade , Superantígenos/toxicidade , Animais , Western Blotting , Catequina/química , Citocinas/sangue , Citocinas/genética , Dermatite Atópica/imunologia , Relação Dose-Resposta a Droga , Feminino , Galactosamina/imunologia , Galactosamina/farmacologia , Leucócitos Mononucleares/fisiologia , Camundongos , Camundongos Endogâmicos BALB C , RNA Mensageiro/análise , Chá
3.
J Am Acad Dermatol ; 47(2 Suppl): S183-6, 2002 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12140457

RESUMO

Pagetoid reticulosis consists of 2 types: Woringer-Kolopp and Ketron-Goodman disease (K-G). Compared with the former, K-G may have disseminated lesions and a guarded prognosis. We encountered a case of K-G in a 67-year-old man with disseminated plaques on the neck, the trunk, and both extremities. Histologic specimens demonstrated medium- to large-sized, atypical cells infiltrating in the lower epidermis. The phenotype (CD3(+), CD4(-), CD8(-), CD45RO(-), CD45RA(+)) and ultrastructural findings suggest that these cells were immature T cells. Although PUVA was initially effective, new plaques in which atypical cells are still present histologically, have appeared through a 6-year follow-up. Literature review revealed the high rate of recurrence. These findings suggest that K-G is an epidermotropic or immature T-cell variant of mycosis fungoides. In patients with K-G, therefore, long-term observation is necessary: Disappearance of cutaneous lesions may not mean cure.


Assuntos
Doenças Linfáticas , Neoplasias Cutâneas , Idoso , Idoso de 80 Anos ou mais , Seguimentos , Humanos , Imuno-Histoquímica , Doenças Linfáticas/tratamento farmacológico , Doenças Linfáticas/patologia , Masculino , Recidiva Local de Neoplasia , Terapia PUVA , Pele/patologia , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia
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