Low-dose Selumetinib for the Treatment of Plexiform Neurofibromas in Chinese Children

Inclusion Criteria:

* Male and females;
* Between 3 and 18 years of age;
* Diagnosis of NF1 as determined by meeting at least 2 of the following 7 criteria: (1) six or more cafe-au-lait macules (greater than or equal to 0.5cm in prepubertal subjects or greater than or equal to1.5 cm in post pubertal subjects); (2) two or more neurofibromas (any type); (3) freckling in axilla or groin; (4) optic glioma; (5) two or more Lisch nodules; (6) a distinctive bony lesion (dysplasia of the sphenoid bone or dysplasia or thinning of long bone cortex); (7) a first-degree relative with NF1;
* Diagnosis of PN as determined by biopsy and pathological diagnosis;
* Complete resection of PN is not feasible without significant morbidity risk;
* Normal liver, kidney, and heart function;
* Previous treatment, last dose time: colony stimulating factor≥1 week, radiotherapy≥6 weeks, other study drugs\>30 days;
* Able to undergo MRI evaluation;
* Consent of parents (or the person with parental authority in families): signed and dated written informed consent.

Exclusion Criteria:

* Patients with contraindications to selumetinib administration (e.g., allergy to selumetinib);
* Unable to swallow the entire selumetinib capsule;
* Ongoing hormone, immunotherapy, or chemotherapy for PN;
* Previously received multiple myelosuppressive chemotherapy regimens;
* Suffering from other severe and/or uncontrolled systemic diseases not related to NF1 (e.g., uncontrolled diabetes, hypertension, severe malnutrition, chronic liver or kidney disease, active gastrointestinal ulcers, etc.);
* Presence of optic nerve glioma, malignant glioma, malignant peripheral nerve sheath tumor, or other cancers requiring chemotherapy or radiotherapy;
* Presence of severe local or systemic uncontrolled infections;
* Impaired gastrointestinal function or chronic gastrointestinal diseases that may significantly affect the absorption of selumetinib;
* Patients with inadequate liver function: total bilirubin higher than or equal to 1.5 × the upper limit of the normal (ULN) for age and alanine aminotransferase and aspartate aminotransferase higher than or equal to 2.5 × the ULN for age;
* Patients with inadequate renal function: 3-5 years of age maximum serum creatinine (mg/dL) of 0.8; 6-10 years of age maximum serum creatinine (mg/dL) of 1.0; 11-18 years of age maximum serum creatinine (mg/dL) of 1.2;
* Insufficient bone marrow function: absolute neutrophil count lower than 1×109/L;
* Patients with cardiac insufficiency: echocardiogram shows abnormal ejection fraction;
* HIV-infected patients or patients with known immunodeficiency;
* Patients with a history of treatment with selumetinib or other MEK inhibitors;
* Patients who are unable to participate in treatment or follow-up evaluation plans during the study;
* Patients who are unable to give informed consent.