title: Trametinib-induced Left Ventricular Dysfunction in a Child With Relapsed Neuroblastoma.
abstract: The MEK inhibitor trametinib is globally approved for metastatic melanoma harboring BRAF mutations. There are no reports thus far on its use in children. Exome sequencing on a relapsed tumor sample from an 11-year-old male with progressive, multiply relapsed stage 4 neuroblastoma revealed NRASQ61K mutation. After demonstration of normal cardiac function, he was started on oral trametinib. On day 13 of treatment, echocardiogram showed moderate left ventricular dysfunction. Trametinib was discontinued on day 15 and oral lisinopril was started. Left ventricular function recovered to baseline 37 days after discontinuing trametinib. However, neuroblastoma showed further progression.
authors.affiliation: *Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY Divisions of †Cardiology ‡Hematology-Oncology, All Children's Hospital, St Petersburg, FL.
authors.forename: Shakeel
authors.initials: S
authors.lastname: Modak
authors.forename: Alfred
authors.initials: A
authors.lastname: Asante-Korang
authors.forename: Laurel J
authors.initials: LJ
authors.lastname: Steinherz
authors.forename: Nanette
authors.initials: N
authors.lastname: Grana
mesh_terms: D002648:Child; D020558:GTP Phosphohydrolases / Q000235:genetics; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D009154:Mutation / Q000235:genetics; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D009447:Neuroblastoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000009:adverse effects*; D011728:Pyridones / Q000009:adverse effects*; D011744:Pyrimidinones / Q000009:adverse effects*; D018487:Ventricular Dysfunction, Left / Q000139:chemically induced* / Q000188:drug therapy / Q000235:genetics
chemical_list: D008565:Membrane Proteins; D047428:Protein Kinase Inhibitors; D011728:Pyridones; D011744:Pyrimidinones; C560077:trametinib; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human