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PLoS One ; 10(4): e0124590, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25897843

RESUMEN

We have previously demonstrated an impact of the BRAF inhibitor vemurafenib on patient lymphocyte counts. In the current study, the extent to which concomitant use of corticosteroids in BRAF inhibitor treated patients affects lymphocyte counts and predisposes to infection was investigated. A cohort of 102 patients receiving either the selective BRAF inhibitor vemurafenib or dabrafenib was analyzed. The amount of patients receiving either medication with or without systemic corticosteroids (dexamethasone) was determined and lymphocyte counts before and under therapy assessed. Additionally, the number and severity of infections occurring in these groups was analyzed. Vemurafenib treatment led to a considerable decrease in lymphocyte cell counts, with 62.3% of patients having lymphopenia. Dabrafenib treated patients only rarely demonstrated lymphopenia (12.5%). Dexamethasone co-administration further diminished lymphocyte counts. Lymphopenias were observed in 84.6% of patients receiving vemurafenib and dexamethasone. In our cohort, infections were noted in 9 patients, 4 of these were severe and 2 eventually fatal. All 9 cases with infections demonstrated lymphopenia, 8 of these had received dexamethasone and 7 of these a therapy with vemurafenib. Our findings demonstrate a significant lymphopenia in patients treated with the BRAF inhibitor vemurafenib, which is further augmented by dexamethasone and predisposes to infection. If validated in other studies, risk of infection should be considered when applying corticosteroids in combination with BRAF inhibitors, in particular vemurafenib.


Asunto(s)
Corticoesteroides/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Dexametasona/efectos adversos , Indoles/efectos adversos , Linfopenia/inducido químicamente , Infecciones Oportunistas/inducido químicamente , Inhibidores de Proteínas Quinasas/efectos adversos , Sulfonamidas/efectos adversos , Corticoesteroides/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Dexametasona/administración & dosificación , Femenino , Expresión Génica , Humanos , Imidazoles/administración & dosificación , Imidazoles/uso terapéutico , Indoles/administración & dosificación , Recuento de Linfocitos , Linfocitos/efectos de los fármacos , Linfocitos/metabolismo , Linfocitos/patología , Linfopenia/genética , Linfopenia/mortalidad , Linfopenia/patología , Masculino , Melanoma/tratamiento farmacológico , Melanoma/genética , Melanoma/mortalidad , Melanoma/patología , Persona de Mediana Edad , Infecciones Oportunistas/genética , Infecciones Oportunistas/mortalidad , Infecciones Oportunistas/patología , Oximas/administración & dosificación , Oximas/uso terapéutico , Inhibidores de Proteínas Quinasas/administración & dosificación , Proteínas Proto-Oncogénicas B-raf/antagonistas & inhibidores , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Proto-Oncogénicas B-raf/metabolismo , Estudios Retrospectivos , Riesgo , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/mortalidad , Neoplasias Cutáneas/patología , Sulfonamidas/administración & dosificación , Análisis de Supervivencia , Vemurafenib
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