Selumetinib Active in Children With Neurofibromatosis Type 1

Selumetinib Active in Children With Neurofibromatosis Type 1
Selumetinib Active in Children With Neurofibromatosis Type 1

(HealthDay News) – The oral selective inhibitor of MAPK kinase 1 and 2, selumetinib, is active in children with neurofibromatosis type 1 and inoperable plexiform neurofibromas, according to a study published in the Dec. 29 issue of the New England Journal of Medicine.

Eva Dombi, MD, from the Center for Cancer Research in Bethesda, MD, and colleagues conducted a phase 1 trial of selumetinib in children with neurofibromatosis type 1 and inoperable plexiform neurofibromas. Selumetinib was administered twice daily at a dose of 20 to 30mg/m² of body-surface area. Selumetinib was also tested using a mouse model of neurofibromatosis type 1-related neurofibroma.

Twenty-four children (median tumor volume, 1,205mL) received selumetinib. The researchers found that children were able to receive selumetinib on a long-term basis, with a median of 30 cycles (range, six to 56 cycles). A dose of 25mg/m² was the maximum tolerated. Acneiform rash, gastrointestinal effects, and asymptomatic creatine kinase elevation were the most common toxic effects associated with selumetinib. Seventeen of the 24 children (71%) had confirmed partial responses with selumetinib treatment; 67% of 18 mice had decreases from baseline in neurofibroma volume. There was no evidence of disease progression to date (tumor volume increase of ≥20% from baseline).

"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," the authors write.

The trial was partially funded by AstraZeneca, which provided the selumetinib.

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