- Authors:
- Eva Dombi,
- Andrea Baldwin,
- Leigh J Marcus,
- Michael J Fisher,
- Brian Weiss,
- AeRang Kim,
- Patricia Whitcomb,
- Staci Martin,
- Lindsey E Aschbacher-Smith,
- Tilat A Rizvi,
- Jianqiang Wu,
- Rachel Ershler,
- Pamela Wolters,
- Janet Therrien,
- John Glod,
- Jean B Belasco,
- Elizabeth Schorry,
- Alessandra Brofferio,
- Amy J Starosta,
- Andrea Gillespie,
- Austin L Doyle,
- Nancy Ratner,
- Brigitte C Widemann
N Engl J Med 2016 12;375(26):2550-2560
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.).
Background: 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.
Methods: 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).
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