sábado, 8 de febrero de 2020

Tratamiento de los cánceres poco comunes en la niñez (PDQ®)–Versión para profesionales de salud - Instituto Nacional del Cáncer

Tratamiento de los cánceres poco comunes en la niñez (PDQ®)–Versión para profesionales de salud - Instituto Nacional del Cáncer

Instituto Nacional Del Cáncer

Tratamiento de los cánceres poco comunes en la niñez (PDQ®)–Versión para profesionales de salud

Vaya a la versión para pacientes

Carcinoma de línea media con alteración del gen NUT (carcinoma de línea media NUT)

Características moleculares

El carcinoma de línea media NUT es una neoplasia maligna muy infrecuente que se define desde el punto de vista genético por reordenamientos del gen NUT. En la mayoría de los casos (75 %), el gen NUT del cromosoma 15q14 se fusiona con el gen BRD4 del cromosoma 19p13; esto crea genes quiméricos que codifican las proteínas de fusión BRD-NUT. En los otros casos, el gen NUT se fusiona con el gen BRD3 del cromosoma 9q34 o el gen NSD3 del cromosoma 8p11;[184] estos casos se conocen como tumores con variante del NUT.[185]

Cuadro clínico inicial y desenlace

Los carcinomas de línea media infantil (carcinomas de línea media NUT) surgen en las estructuras epiteliales de la línea media; por lo general, el mediastino y el tubo aerodigestivo superior, y se manifiestan como carcinomas indiferenciados muy malignos, con diferenciación escamosa o sin esta.[186,187] Aunque la descripción original de esta neoplasia se hizo en niños y adultos jóvenes, afecta a pacientes de todas las edades.[185] En una serie retrospectiva de correlación clinicopatológica, se encontró que la mediana de edad en el momento del diagnóstico de 54 pacientes fue de 16 años (intervalo, 0,1–78 años).[188]
El desenlace es muy precario y la mediana de supervivencia es menor de 1 año. Los datos preliminares indican que los tumores con variante del NUT tienen una evolución más prolongada.[185,186]

Tratamiento del carcinoma de línea media infantil

Las opciones de tratamiento del carcinoma de línea media infantil son las siguientes:
  • Quimioterapia.
  • Cirugía.
  • Radioterapia.
El tratamiento del carcinoma de línea media infantil con alteración del gen NUT (carcinoma de línea media NUT) ha incluido un abordaje multimodal con quimioterapia sistémica, cirugía y radioterapia. Se han utilizado cisplatino, taxanos y alquilantes con cierto éxito; aunque la respuesta temprana es frecuente, la progresión tumoral se presenta pronto durante el curso de la enfermedad.[188,189][Grado de comprobación: 3iiiB] En un informe del NUT Midline Carcinoma Registry, se señaló que 40 pacientes con tumores primarios de cabeza y cuello eran evaluables. La supervivencia general a 2 años fue de 30 %. Los tres sobrevivientes a largo plazo (35, 72 y 78 meses) se sometieron a resección total macroscópica primaria y recibieron terapia adyuvante.[187][Grado de comprobación: 3iiA]
En estudios preclínicos, se observó que la fusión NUT-BRD4 se relacionó con una disminución global de la acetilación de histonas y represión de la transcripción; en los estudios también se observó que es posible restaurar esta acetilación con inhibidores de la histona desacetilasa, que producen diferenciación escamosa e interrupción del crecimiento in vitro, así como inhibición del crecimiento en modelos de xenoinjerto. Se notificó una respuesta al vorinostat en dos casos separados de niños con enfermedad resistente al tratamiento; lo que indica una posible función de esta clase de fármacos para tratar esta neoplasia maligna.[190,191] Los inhibidores del bromodominio BET constituyen una clase de sustancias prometedoras que están en investigación para adultos con esta neoplasia maligna.[184]

Opciones de tratamiento en evaluación para el carcinoma de línea media infantil

La información en inglés sobre los ensayos clínicos patrocinados por el Instituto Nacional del Cáncer (NCI) se encuentra en el portal de Internet del NCI. Para obtener información en inglés sobre ensayos clínicos patrocinados por otras organizaciones, consultar el portal de Internet ClinicalTrials.gov.
A continuación, se presentan ejemplos de ensayos clínicos nacionales o institucionales en curso:
  • APEC1621 (NCT03155620) (Pediatric MATCH: Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients with Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders): en el NCI–Children's Oncology Group Pediatric Molecular Analysis for Therapeutic Choice (MATCH), que se conoce como Pediatric MATCH, se emparejarán fármacos de terapia dirigida con cambios moleculares específicos identificados mediante ensayo de secuenciación dirigida de última generación para más de 4000 mutaciones en más de 160 genes presentes en tumores sólidos resistentes al tratamiento y recidivantes. Los niños y adolescentes de 1 a 21 años son aptos para participar en este ensayo.
    El tejido tumoral de la enfermedad progresiva o recidivante debe estar disponible para la caracterización molecular. Se ofrecerá tratamiento del Pediatric MATCH a los pacientes con tumores de variantes moleculares comprendidas en los grupos de tratamiento del ensayo. Para obtener más información, consultar el portal de Internet del NCI y el portal de Internet ClinicalTrials.gov (en inglés).
  • NCT01587703 (A Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics, and Clinical Activity of GSK525762 in Subjects With NUT Midline Carcinoma and Other Cancers): en este estudio se evalúa la inocuidad, el perfil farmacocinético y farmacodinámico de la administración oral de GSK525762, un inhibidor del bromodominio BET, así como su tolerabilidad y la actividad clínica en pacientes con carcinoma de línea media NUT y otros tumores sólidos. Son aptos para participar en este estudio los pacientes de 16 años y más.
  • NCT01987362 (A Two Part, Multicenter, Open-label Study of TEN-010 Given Subcutaneously): este es un estudio multicéntrico de fase I, no aleatorizado, con aumento escalonado de las dosis y sin anonimato con la participación de pacientes de 18 años o más con tumores sólidos en estadio avanzado confirmados con pruebas histológicas cuya enfermedad sea progresiva y necesiten tratamiento, o pacientes de carcinoma de la línea media NUT. En este estudio, se evalúa la inocuidad, la tolerabilidad y las características farmacocinéticas de TEN-010, un inhibidor del bromodominio micromolecular.
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