RESUMO
EGFR overexpression in salivary gland carcinomas provides the rational for the investigation of anti-EGFR treatments in recurrent and/or metastatic salivary gland cancers (RMSGCs). The activity of cetuximab in terms of clinical benefit rate (CBR) defined as the occurrence of objective response (CR or PR) or stable disease (SD) for >or=6months was investigated. From April to December 2005, 30 patients [23 adenoid cystic carcinoma (ACC) and 7 non-ACC] were treated with cetuximab at 400mg/m(2)/week followed by 250mg/m(2)/week until progression, major toxicity or voluntary discontinuation. EGFR expression and gene status were retrospectively analyzed by immunocytochemistry and fluorescence in situ hybridization, respectively. A median of 14 courses of cetuximab (range 5-54) were infused. Skin toxicity was the main adverse event. Cetuximab provides a CBR in 50% (95% CL, 31 to 69%) of cases. None tumor sample showed EGFR gene amplification and an increased EGFR copy number was observed in 12% of samples, all ACC. Skin rash >or=G2, EGFR overexpression and EGFR copy number were not statistically correlated to CB. In RMSGCs further evaluations of EGFR targeting agents are advisable and should take place by appropriate tumor biological selection, differentiating ACC from non-ACC.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Carcinoma Adenoide Cístico/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias das Glândulas Salivares/tratamento farmacológico , Adolescente , Adulto , Idoso , Anticorpos Monoclonais Humanizados , Carcinoma Adenoide Cístico/metabolismo , Carcinoma Adenoide Cístico/secundário , Cetuximab , Intervalo Livre de Doença , Receptores ErbB/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/metabolismo , Cuidados Paliativos/métodos , Estudos Retrospectivos , Neoplasias das Glândulas Salivares/genética , Neoplasias das Glândulas Salivares/metabolismo , Adulto JovemAssuntos
Anticorpos Monoclonais/efeitos adversos , Antineoplásicos/efeitos adversos , Toxidermias/etiologia , Receptores ErbB/antagonistas & inibidores , Neoplasias/tratamento farmacológico , Pele/efeitos dos fármacos , Pele/efeitos da radiação , Anticorpos Monoclonais Humanizados , Cetuximab , Terapia Combinada , Relação Dose-Resposta à Radiação , Toxidermias/patologia , Receptores ErbB/metabolismo , Humanos , Neoplasias/metabolismo , Neoplasias/radioterapia , Pele/metabolismo , Pele/patologia , Fatores de Tempo , Resultado do TratamentoRESUMO
Previous reports demonstrate a circadian rhythm of the free thyroid hormones in healthy subjects. In this study we evaluated circadian variation of FT3 and FT4 in hyperthyroid and hypothyroid states. We considered six hyperthyroid patients, six hypothyroid patients and six control subjects. Blood samples were taken two hours apart from a catherterized arm vein. Data were evaluated by Halberg's cosinor analysis. The results show that FT3 and FT4 exhibit a circadian rhythm in healthy subjects, not evident in hyperthyroid and hypothyroid patients.