Alectinib

alectinib

An orally available inhibitor of the receptor tyrosine kinase anaplastic lymphoma kinase (ALK) with antineoplastic activity. Upon administration, alectinib binds to and inhibits ALK kinase, ALK fusion proteins as well as the gatekeeper mutation ALKL1196M known as one of the mechanisms of acquired resistance to small-molecule kinase inhibitors. The inhibition leads to disruption of ALK-mediated signaling and eventually inhibits tumor cell growth in ALK-overexpressing tumor cells. ALK belongs to the insulin receptor superfamily and plays an important role in nervous system development. ALK dysregulation and gene rearrangements are associated with a series of tumors.

Clinical use of Alectinib

Alectinib is a tyrosine kinase receptor inhibitor and antineoplastic agent used in the therapy of selected forms of advanced non-small cell lung cancer.  

Liver safety of Alectinib

Alectinib is associated with a moderate rate of transient elevations in serum aminotransferase levels during therapy and with rare instances of clinically apparent acute liver injury. 

Mechanism of action of Alectinib

Alectinib (al ek' ti nib) is a small molecule tyrosine kinase receptor inhibitor with potent activity against anaplastic lymphoma kinase (ALK) that is rearranged and mutated in slective cancers, including approximately 5% of non-small cell lung cancer (NSCLC).  The mutated, rearranged ALK promotes unregulated cell growth and proliferation and is sometimes overexpressed in cancer cells.  Alectinib has been found to inhibit mutated ALK in cell culture and in several clinical trials was found to induce objective responses in a proportion of patients with refractory, advanced NSCLC that are ALK-positive. 

FDA approval information for Alectinib

Alectinib was approved for use in the United States in 2015 in patients with ALK-positive, metastatic NSCLC who have progressed despite therapy with first generation ALK inhibitors (such as crizotinib). 

Dosage and administration for Alectinib

Alectinib is available in capsules of 150 mg under the brand name Alecensa.  The recommended dose is 600 mg twice daily, continued until disease progression or intolerable toxicity occurs. 

Side effects of Alectinib

Side effects are common and can include fatigue, constipation, peripheral edema and myalgia.  Uncommon, but potentially severe side effects include interstitial lung disease, severe myopathy, bradycardia and fetal toxicity. 

 

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