Selumetinib is a MEK1/2 inhibitor developed by AstraZeneca and approved by the US FDA in April 2020 for the treatment of neurofibromatosis type 1 (NF1)-associated plexiform neurofibromas in children aged 2 years and older. The drug works by selectively inhibiting MEK protein kinase and is the first targeted drug approved for the treatment of this rare disease.

The role and efficacy of Selumetinib

Selumetinib is an innovative targeted drug with a unique mechanism of action that provides a new treatment option for patients with NF1-related plexiform neurofibroma, which can effectively reduce tumor volume and improve clinical symptoms.

Pharmacological mechanism of action

Selumetinib blocks the RAS/MAPK signaling pathway by specifically inhibiting MEK1/2 protein kinase activity. This pathway plays a key role in the growth of NF1-associated tumors, and drugs can significantly slow tumor progression.

Clinical treatment effect

Clinical trials have shown that about 66% of patients have tumors that shrink by ≥20% after treatment. Most patients have improved symptoms, including pain reduction and functional recovery, and the effect of treatment usually begins to appear after 12 weeks of treatment.

The drug has not yet been officially marketed in China, and is currently mainly obtained through special channels.

Dosage of Selumetinib dosage

The use of Selumetinib needs to strictly follow the standard medication regimen, and the correct dosage directly affects the therapeutic effect and safety.

Standard dosing regimen

The recommended dose is 25mg/㎡, orally twice a day (about 12 hours apart). The dose should be calculated accurately based on body surface area, with a maximum single dose not exceeding 50 mg.

Dosage requirements

It must be taken on an empty stomach and fasted 2 hours before each dose and 1 hour after taking the medicine. The drug should be swallowed whole, not crushed or chewed. If the next dose is less than 6 hours before the next dose, skip it.

Principle of dose adjustment

In the case of grade 2 toxicity, the dose should be reduced by 20%, and the dose of grade 3 toxicity should be suspended until it recovers to grade ≤ 1, and the dose reduction of 40% will continue. Grade 4 toxicity usually requires permanent discontinuation.

Tumor response and drug tolerance should be assessed regularly during treatment.

Side effects and precautions of Selumetinib

Selumetinib may cause a variety of adverse effects, and understanding these risks can help with early identification and timely treatment. Rational use of medication can minimize the incidence of adverse reactions.

Common adverse reactions

The most common side effects included vomiting (80%), rash (78%), diarrhea (73%), and nausea (60%). Most are grade 1 to 2 and can be relieved by symptomatic management. About 15% of patients need to be reduced due to adverse effects.

Serious Risk Warning

May cause decreased left ventricular ejection fraction (LVEF), retinopathy, and elevated CPK. Cardiac function tests, visual acuity, and CPK monitoring are done regularly. If you have symptoms, you should seek medical attention immediately.

Growth and development should be monitored for children taking medication. Women of childbearing age should use reliable contraception. Patients with hepatic and renal insufficiency require dose adjustment. Drug interactions are common, and concomitant use of other drugs requires consultation with a doctor.