title: Activity of Selumetinib in Neurofibromatosis Type 1-Related Plexiform Neurofibromas.
abstract: Effective medical therapies are lacking for the treatment of neurofibromatosis type 1-related plexiform neurofibromas, which are characterized by elevated RAS-mitogen-activated protein kinase (MAPK) signaling.
  
  
  
  We conducted a phase 1 trial of selumetinib (AZD6244 or ARRY-142886), an oral selective inhibitor of MAPK kinase (MEK) 1 and 2, in children who had neurofibromatosis type 1 and inoperable plexiform neurofibromas to determine the maximum tolerated dose and to evaluate plasma pharmacokinetics. Selumetinib was administered twice daily at a dose of 20 to 30 mg per square meter of body-surface area on a continuous dosing schedule (in 28-day cycles). We also tested selumetinib using a mouse model of neurofibromatosis type 1-related neurofibroma. Response to treatment (i.e., an increase or decrease from baseline in the volume of plexiform neurofibromas) was monitored by using volumetric magnetic resonance imaging analysis to measure the change in size of the plexiform neurofibroma.
  
  
  
  A total of 24 children (median age, 10.9 years; range, 3.0 to 18.5) with a median tumor volume of 1205 ml (range, 29 to 8744) received selumetinib. Patients were able to receive selumetinib on a long-term basis; the median number of cycles was 30 (range, 6 to 56). The maximum tolerated dose was 25 mg per square meter (approximately 60% of the recommended adult dose). The most common toxic effects associated with selumetinib included acneiform rash, gastrointestinal effects, and asymptomatic creatine kinase elevation. The results of pharmacokinetic evaluations of selumetinib among the children in this trial were similar to those published for adults. Treatment with selumetinib resulted in confirmed partial responses (tumor volume decreases from baseline of ≥20%) in 17 of the 24 children (71%) and decreases from baseline in neurofibroma volume in 12 of 18 mice (67%). Disease progression (tumor volume increase from baseline of ≥20%) has not been observed to date. Anecdotal evidence of decreases in tumor-related pain, disfigurement, and functional impairment was observed.
  
  
  
  Our early-phase data suggested that children with neurofibromatosis type 1 and inoperable plexiform neurofibromas benefited from long-term dose-adjusted treatment with selumetinib without having excess toxic effects. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT01362803 .).
authors.affiliation: From the Center for Cancer Research, Pediatric Oncology Branch, Bethesda (E.D., A. Baldwin, L.J.M., P. Whitcomb, S.M., R.E., P. Wolters, J.T., J.G., A.J.S., A.G., B.C.W.) and the Cancer Therapy Evaluation Program, Shady Grove (A.L.D.), National Cancer Institute, and the National Heart, Lung, and Blood Institute (A. Brofferio), Bethesda, National Institutes of Health, and the Food and Drug Administration, Silver Spring (L.J.M., R.E.) - all in Maryland; the Division of Oncology, Children's Hospital of Philadelphia, and the Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia (M.J.F., J.B.B.); Children's National Health System, Washington, DC (A.K.); and Cincinnati Children's Hospital, Cincinnati (B.W., L.E.A.-S., T.A.R., J.W., E.S., N.R.).
authors.forename: Eva
authors.initials: E
authors.lastname: Dombi
authors.affiliation: From the Center for Cancer Research, Pediatric Oncology Branch, Bethesda (E.D., A. Baldwin, L.J.M., P. Whitcomb, S.M., R.E., P. Wolters, J.T., J.G., A.J.S., A.G., B.C.W.) and the Cancer Therapy Evaluation Program, Shady Grove (A.L.D.), National Cancer Institute, and the National Heart, Lung, and Blood Institute (A. Brofferio), Bethesda, National Institutes of Health, and the Food and Drug Administration, Silver Spring (L.J.M., R.E.) - all in Maryland; the Division of Oncology, Children's Hospital of Philadelphia, and the Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia (M.J.F., J.B.B.); Children's National Health System, Washington, DC (A.K.); and Cincinnati Children's Hospital, Cincinnati (B.W., L.E.A.-S., T.A.R., J.W., E.S., N.R.).
authors.forename: Andrea
authors.initials: A
authors.lastname: Baldwin
authors.affiliation: From the Center for Cancer Research, Pediatric Oncology Branch, Bethesda (E.D., A. Baldwin, L.J.M., P. Whitcomb, S.M., R.E., P. Wolters, J.T., J.G., A.J.S., A.G., B.C.W.) and the Cancer Therapy Evaluation Program, Shady Grove (A.L.D.), National Cancer Institute, and the National Heart, Lung, and Blood Institute (A. Brofferio), Bethesda, National Institutes of Health, and the Food and Drug Administration, Silver Spring (L.J.M., R.E.) - all in Maryland; the Division of Oncology, Children's Hospital of Philadelphia, and the Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia (M.J.F., J.B.B.); Children's National Health System, Washington, DC (A.K.); and Cincinnati Children's Hospital, Cincinnati (B.W., L.E.A.-S., T.A.R., J.W., E.S., N.R.).
authors.forename: Leigh J
authors.initials: LJ
authors.lastname: Marcus
authors.affiliation: From the Center for Cancer Research, Pediatric Oncology Branch, Bethesda (E.D., A. Baldwin, L.J.M., P. Whitcomb, S.M., R.E., P. Wolters, J.T., J.G., A.J.S., A.G., B.C.W.) and the Cancer Therapy Evaluation Program, Shady Grove (A.L.D.), National Cancer Institute, and the National Heart, Lung, and Blood Institute (A. Brofferio), Bethesda, National Institutes of Health, and the Food and Drug Administration, Silver Spring (L.J.M., R.E.) - all in Maryland; the Division of Oncology, Children's Hospital of Philadelphia, and the Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia (M.J.F., J.B.B.); Children's National Health System, Washington, DC (A.K.); and Cincinnati Children's Hospital, Cincinnati (B.W., L.E.A.-S., T.A.R., J.W., E.S., N.R.).
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Fisher
authors.affiliation: From the Center for Cancer Research, Pediatric Oncology Branch, Bethesda (E.D., A. Baldwin, L.J.M., P. Whitcomb, S.M., R.E., P. Wolters, J.T., J.G., A.J.S., A.G., B.C.W.) and the Cancer Therapy Evaluation Program, Shady Grove (A.L.D.), National Cancer Institute, and the National Heart, Lung, and Blood Institute (A. Brofferio), Bethesda, National Institutes of Health, and the Food and Drug Administration, Silver Spring (L.J.M., R.E.) - all in Maryland; the Division of Oncology, Children's Hospital of Philadelphia, and the Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia (M.J.F., J.B.B.); Children's National Health System, Washington, DC (A.K.); and Cincinnati Children's Hospital, Cincinnati (B.W., L.E.A.-S., T.A.R., J.W., E.S., N.R.).
authors.forename: Brian
authors.initials: B
authors.lastname: Weiss
authors.affiliation: From the Center for Cancer Research, Pediatric Oncology Branch, Bethesda (E.D., A. Baldwin, L.J.M., P. Whitcomb, S.M., R.E., P. Wolters, J.T., J.G., A.J.S., A.G., B.C.W.) and the Cancer Therapy Evaluation Program, Shady Grove (A.L.D.), National Cancer Institute, and the National Heart, Lung, and Blood Institute (A. Brofferio), Bethesda, National Institutes of Health, and the Food and Drug Administration, Silver Spring (L.J.M., R.E.) - all in Maryland; the Division of Oncology, Children's Hospital of Philadelphia, and the Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia (M.J.F., J.B.B.); Children's National Health System, Washington, DC (A.K.); and Cincinnati Children's Hospital, Cincinnati (B.W., L.E.A.-S., T.A.R., J.W., E.S., N.R.).
authors.forename: AeRang
authors.initials: A
authors.lastname: Kim
authors.affiliation: From the Center for Cancer Research, Pediatric Oncology Branch, Bethesda (E.D., A. Baldwin, L.J.M., P. Whitcomb, S.M., R.E., P. Wolters, J.T., J.G., A.J.S., A.G., B.C.W.) and the Cancer Therapy Evaluation Program, Shady Grove (A.L.D.), National Cancer Institute, and the National Heart, Lung, and Blood Institute (A. Brofferio), Bethesda, National Institutes of Health, and the Food and Drug Administration, Silver Spring (L.J.M., R.E.) - all in Maryland; the Division of Oncology, Children's Hospital of Philadelphia, and the Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia (M.J.F., J.B.B.); Children's National Health System, Washington, DC (A.K.); and Cincinnati Children's Hospital, Cincinnati (B.W., L.E.A.-S., T.A.R., J.W., E.S., N.R.).
authors.forename: Patricia
authors.initials: P
authors.lastname: Whitcomb
authors.affiliation: From the Center for Cancer Research, Pediatric Oncology Branch, Bethesda (E.D., A. Baldwin, L.J.M., P. Whitcomb, S.M., R.E., P. Wolters, J.T., J.G., A.J.S., A.G., B.C.W.) and the Cancer Therapy Evaluation Program, Shady Grove (A.L.D.), National Cancer Institute, and the National Heart, Lung, and Blood Institute (A. Brofferio), Bethesda, National Institutes of Health, and the Food and Drug Administration, Silver Spring (L.J.M., R.E.) - all in Maryland; the Division of Oncology, Children's Hospital of Philadelphia, and the Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia (M.J.F., J.B.B.); Children's National Health System, Washington, DC (A.K.); and Cincinnati Children's Hospital, Cincinnati (B.W., L.E.A.-S., T.A.R., J.W., E.S., N.R.).
authors.forename: Staci
authors.initials: S
authors.lastname: Martin
authors.affiliation: From the Center for Cancer Research, Pediatric Oncology Branch, Bethesda (E.D., A. Baldwin, L.J.M., P. Whitcomb, S.M., R.E., P. Wolters, J.T., J.G., A.J.S., A.G., B.C.W.) and the Cancer Therapy Evaluation Program, Shady Grove (A.L.D.), National Cancer Institute, and the National Heart, Lung, and Blood Institute (A. Brofferio), Bethesda, National Institutes of Health, and the Food and Drug Administration, Silver Spring (L.J.M., R.E.) - all in Maryland; the Division of Oncology, Children's Hospital of Philadelphia, and the Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia (M.J.F., J.B.B.); Children's National Health System, Washington, DC (A.K.); and Cincinnati Children's Hospital, Cincinnati (B.W., L.E.A.-S., T.A.R., J.W., E.S., N.R.).
authors.forename: Lindsey E
authors.initials: LE
authors.lastname: Aschbacher-Smith
authors.affiliation: From the Center for Cancer Research, Pediatric Oncology Branch, Bethesda (E.D., A. Baldwin, L.J.M., P. Whitcomb, S.M., R.E., P. Wolters, J.T., J.G., A.J.S., A.G., B.C.W.) and the Cancer Therapy Evaluation Program, Shady Grove (A.L.D.), National Cancer Institute, and the National Heart, Lung, and Blood Institute (A. Brofferio), Bethesda, National Institutes of Health, and the Food and Drug Administration, Silver Spring (L.J.M., R.E.) - all in Maryland; the Division of Oncology, Children's Hospital of Philadelphia, and the Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia (M.J.F., J.B.B.); Children's National Health System, Washington, DC (A.K.); and Cincinnati Children's Hospital, Cincinnati (B.W., L.E.A.-S., T.A.R., J.W., E.S., N.R.).
authors.forename: Tilat A
authors.initials: TA
authors.lastname: Rizvi
authors.affiliation: From the Center for Cancer Research, Pediatric Oncology Branch, Bethesda (E.D., A. Baldwin, L.J.M., P. Whitcomb, S.M., R.E., P. Wolters, J.T., J.G., A.J.S., A.G., B.C.W.) and the Cancer Therapy Evaluation Program, Shady Grove (A.L.D.), National Cancer Institute, and the National Heart, Lung, and Blood Institute (A. Brofferio), Bethesda, National Institutes of Health, and the Food and Drug Administration, Silver Spring (L.J.M., R.E.) - all in Maryland; the Division of Oncology, Children's Hospital of Philadelphia, and the Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia (M.J.F., J.B.B.); Children's National Health System, Washington, DC (A.K.); and Cincinnati Children's Hospital, Cincinnati (B.W., L.E.A.-S., T.A.R., J.W., E.S., N.R.).
authors.forename: Jianqiang
authors.initials: J
authors.lastname: Wu
authors.affiliation: From the Center for Cancer Research, Pediatric Oncology Branch, Bethesda (E.D., A. Baldwin, L.J.M., P. Whitcomb, S.M., R.E., P. Wolters, J.T., J.G., A.J.S., A.G., B.C.W.) and the Cancer Therapy Evaluation Program, Shady Grove (A.L.D.), National Cancer Institute, and the National Heart, Lung, and Blood Institute (A. Brofferio), Bethesda, National Institutes of Health, and the Food and Drug Administration, Silver Spring (L.J.M., R.E.) - all in Maryland; the Division of Oncology, Children's Hospital of Philadelphia, and the Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia (M.J.F., J.B.B.); Children's National Health System, Washington, DC (A.K.); and Cincinnati Children's Hospital, Cincinnati (B.W., L.E.A.-S., T.A.R., J.W., E.S., N.R.).
authors.forename: Rachel
authors.initials: R
authors.lastname: Ershler
authors.affiliation: From the Center for Cancer Research, Pediatric Oncology Branch, Bethesda (E.D., A. Baldwin, L.J.M., P. Whitcomb, S.M., R.E., P. Wolters, J.T., J.G., A.J.S., A.G., B.C.W.) and the Cancer Therapy Evaluation Program, Shady Grove (A.L.D.), National Cancer Institute, and the National Heart, Lung, and Blood Institute (A. Brofferio), Bethesda, National Institutes of Health, and the Food and Drug Administration, Silver Spring (L.J.M., R.E.) - all in Maryland; the Division of Oncology, Children's Hospital of Philadelphia, and the Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia (M.J.F., J.B.B.); Children's National Health System, Washington, DC (A.K.); and Cincinnati Children's Hospital, Cincinnati (B.W., L.E.A.-S., T.A.R., J.W., E.S., N.R.).
authors.forename: Pamela
authors.initials: P
authors.lastname: Wolters
authors.affiliation: From the Center for Cancer Research, Pediatric Oncology Branch, Bethesda (E.D., A. Baldwin, L.J.M., P. Whitcomb, S.M., R.E., P. Wolters, J.T., J.G., A.J.S., A.G., B.C.W.) and the Cancer Therapy Evaluation Program, Shady Grove (A.L.D.), National Cancer Institute, and the National Heart, Lung, and Blood Institute (A. Brofferio), Bethesda, National Institutes of Health, and the Food and Drug Administration, Silver Spring (L.J.M., R.E.) - all in Maryland; the Division of Oncology, Children's Hospital of Philadelphia, and the Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia (M.J.F., J.B.B.); Children's National Health System, Washington, DC (A.K.); and Cincinnati Children's Hospital, Cincinnati (B.W., L.E.A.-S., T.A.R., J.W., E.S., N.R.).
authors.forename: Janet
authors.initials: J
authors.lastname: Therrien
authors.affiliation: From the Center for Cancer Research, Pediatric Oncology Branch, Bethesda (E.D., A. Baldwin, L.J.M., P. Whitcomb, S.M., R.E., P. Wolters, J.T., J.G., A.J.S., A.G., B.C.W.) and the Cancer Therapy Evaluation Program, Shady Grove (A.L.D.), National Cancer Institute, and the National Heart, Lung, and Blood Institute (A. Brofferio), Bethesda, National Institutes of Health, and the Food and Drug Administration, Silver Spring (L.J.M., R.E.) - all in Maryland; the Division of Oncology, Children's Hospital of Philadelphia, and the Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia (M.J.F., J.B.B.); Children's National Health System, Washington, DC (A.K.); and Cincinnati Children's Hospital, Cincinnati (B.W., L.E.A.-S., T.A.R., J.W., E.S., N.R.).
authors.forename: John
authors.initials: J
authors.lastname: Glod
authors.affiliation: From the Center for Cancer Research, Pediatric Oncology Branch, Bethesda (E.D., A. Baldwin, L.J.M., P. Whitcomb, S.M., R.E., P. Wolters, J.T., J.G., A.J.S., A.G., B.C.W.) and the Cancer Therapy Evaluation Program, Shady Grove (A.L.D.), National Cancer Institute, and the National Heart, Lung, and Blood Institute (A. Brofferio), Bethesda, National Institutes of Health, and the Food and Drug Administration, Silver Spring (L.J.M., R.E.) - all in Maryland; the Division of Oncology, Children's Hospital of Philadelphia, and the Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia (M.J.F., J.B.B.); Children's National Health System, Washington, DC (A.K.); and Cincinnati Children's Hospital, Cincinnati (B.W., L.E.A.-S., T.A.R., J.W., E.S., N.R.).
authors.forename: Jean B
authors.initials: JB
authors.lastname: Belasco
authors.affiliation: From the Center for Cancer Research, Pediatric Oncology Branch, Bethesda (E.D., A. Baldwin, L.J.M., P. Whitcomb, S.M., R.E., P. Wolters, J.T., J.G., A.J.S., A.G., B.C.W.) and the Cancer Therapy Evaluation Program, Shady Grove (A.L.D.), National Cancer Institute, and the National Heart, Lung, and Blood Institute (A. Brofferio), Bethesda, National Institutes of Health, and the Food and Drug Administration, Silver Spring (L.J.M., R.E.) - all in Maryland; the Division of Oncology, Children's Hospital of Philadelphia, and the Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia (M.J.F., J.B.B.); Children's National Health System, Washington, DC (A.K.); and Cincinnati Children's Hospital, Cincinnati (B.W., L.E.A.-S., T.A.R., J.W., E.S., N.R.).
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Schorry
authors.affiliation: From the Center for Cancer Research, Pediatric Oncology Branch, Bethesda (E.D., A. Baldwin, L.J.M., P. Whitcomb, S.M., R.E., P. Wolters, J.T., J.G., A.J.S., A.G., B.C.W.) and the Cancer Therapy Evaluation Program, Shady Grove (A.L.D.), National Cancer Institute, and the National Heart, Lung, and Blood Institute (A. Brofferio), Bethesda, National Institutes of Health, and the Food and Drug Administration, Silver Spring (L.J.M., R.E.) - all in Maryland; the Division of Oncology, Children's Hospital of Philadelphia, and the Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia (M.J.F., J.B.B.); Children's National Health System, Washington, DC (A.K.); and Cincinnati Children's Hospital, Cincinnati (B.W., L.E.A.-S., T.A.R., J.W., E.S., N.R.).
authors.forename: Alessandra
authors.initials: A
authors.lastname: Brofferio
authors.affiliation: From the Center for Cancer Research, Pediatric Oncology Branch, Bethesda (E.D., A. Baldwin, L.J.M., P. Whitcomb, S.M., R.E., P. Wolters, J.T., J.G., A.J.S., A.G., B.C.W.) and the Cancer Therapy Evaluation Program, Shady Grove (A.L.D.), National Cancer Institute, and the National Heart, Lung, and Blood Institute (A. Brofferio), Bethesda, National Institutes of Health, and the Food and Drug Administration, Silver Spring (L.J.M., R.E.) - all in Maryland; the Division of Oncology, Children's Hospital of Philadelphia, and the Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia (M.J.F., J.B.B.); Children's National Health System, Washington, DC (A.K.); and Cincinnati Children's Hospital, Cincinnati (B.W., L.E.A.-S., T.A.R., J.W., E.S., N.R.).
authors.forename: Amy J
authors.initials: AJ
authors.lastname: Starosta
authors.affiliation: From the Center for Cancer Research, Pediatric Oncology Branch, Bethesda (E.D., A. Baldwin, L.J.M., P. Whitcomb, S.M., R.E., P. Wolters, J.T., J.G., A.J.S., A.G., B.C.W.) and the Cancer Therapy Evaluation Program, Shady Grove (A.L.D.), National Cancer Institute, and the National Heart, Lung, and Blood Institute (A. Brofferio), Bethesda, National Institutes of Health, and the Food and Drug Administration, Silver Spring (L.J.M., R.E.) - all in Maryland; the Division of Oncology, Children's Hospital of Philadelphia, and the Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia (M.J.F., J.B.B.); Children's National Health System, Washington, DC (A.K.); and Cincinnati Children's Hospital, Cincinnati (B.W., L.E.A.-S., T.A.R., J.W., E.S., N.R.).
authors.forename: Andrea
authors.initials: A
authors.lastname: Gillespie
authors.affiliation: From the Center for Cancer Research, Pediatric Oncology Branch, Bethesda (E.D., A. Baldwin, L.J.M., P. Whitcomb, S.M., R.E., P. Wolters, J.T., J.G., A.J.S., A.G., B.C.W.) and the Cancer Therapy Evaluation Program, Shady Grove (A.L.D.), National Cancer Institute, and the National Heart, Lung, and Blood Institute (A. Brofferio), Bethesda, National Institutes of Health, and the Food and Drug Administration, Silver Spring (L.J.M., R.E.) - all in Maryland; the Division of Oncology, Children's Hospital of Philadelphia, and the Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia (M.J.F., J.B.B.); Children's National Health System, Washington, DC (A.K.); and Cincinnati Children's Hospital, Cincinnati (B.W., L.E.A.-S., T.A.R., J.W., E.S., N.R.).
authors.forename: Austin L
authors.initials: AL
authors.lastname: Doyle
authors.affiliation: From the Center for Cancer Research, Pediatric Oncology Branch, Bethesda (E.D., A. Baldwin, L.J.M., P. Whitcomb, S.M., R.E., P. Wolters, J.T., J.G., A.J.S., A.G., B.C.W.) and the Cancer Therapy Evaluation Program, Shady Grove (A.L.D.), National Cancer Institute, and the National Heart, Lung, and Blood Institute (A. Brofferio), Bethesda, National Institutes of Health, and the Food and Drug Administration, Silver Spring (L.J.M., R.E.) - all in Maryland; the Division of Oncology, Children's Hospital of Philadelphia, and the Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia (M.J.F., J.B.B.); Children's National Health System, Washington, DC (A.K.); and Cincinnati Children's Hospital, Cincinnati (B.W., L.E.A.-S., T.A.R., J.W., E.S., N.R.).
authors.forename: Nancy
authors.initials: N
authors.lastname: Ratner
authors.affiliation: From the Center for Cancer Research, Pediatric Oncology Branch, Bethesda (E.D., A. Baldwin, L.J.M., P. Whitcomb, S.M., R.E., P. Wolters, J.T., J.G., A.J.S., A.G., B.C.W.) and the Cancer Therapy Evaluation Program, Shady Grove (A.L.D.), National Cancer Institute, and the National Heart, Lung, and Blood Institute (A. Brofferio), Bethesda, National Institutes of Health, and the Food and Drug Administration, Silver Spring (L.J.M., R.E.) - all in Maryland; the Division of Oncology, Children's Hospital of Philadelphia, and the Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia (M.J.F., J.B.B.); Children's National Health System, Washington, DC (A.K.); and Cincinnati Children's Hospital, Cincinnati (B.W., L.E.A.-S., T.A.R., J.W., E.S., N.R.).
authors.forename: Brigitte C
authors.initials: BC
authors.lastname: Widemann
mesh_terms: D000293:Adolescent; D000818:Animals; D001562:Benzimidazoles / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D002648:Child; D002675:Child, Preschool; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors*; D018318:Neurofibroma, Plexiform / Q000000981:diagnostic imaging / Q000188:drug therapy*; D009456:Neurofibromatosis 1 / Q000188:drug therapy*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*
chemical_list: C517975:AZD 6244; D001562:Benzimidazoles; D047428:Protein Kinase Inhibitors; D020929:Mitogen-Activated Protein Kinase Kinases