- Class: Tyrosine kinase inhibitor – ALK inhibitor (small molecule, second-generation)
Mechanism of Action (MOA)
- Inhibits anaplastic lymphoma kinase (ALK) tyrosine kinase → blocks ALK-driven signaling pathways (RAS/RAF/MEK/ERK, PI3K/AKT, JAK/STAT).
- Leads to cell cycle arrest and apoptosis in ALK-positive tumor cells.
- Active against tumors resistant to crizotinib (first-generation ALK inhibitor).
Clinical Uses
- ALK-positive metastatic non-small cell lung cancer (NSCLC):
- First-line therapy or after progression on crizotinib.
- Investigational use in other ALK-positive malignancies.
Dosing (Adults)
- 450–750 mg orally once daily (dose depends on formulation and tolerance).
- Administer on an empty stomach (≥2 hours before or after food) to reduce gastrointestinal toxicity.
- Dose reductions required for hepatotoxicity or severe GI toxicity.
Toxicities
- Gastrointestinal: diarrhea, nausea, vomiting, abdominal pain (very common).
- Hepatotoxicity: ↑ AST/ALT, bilirubin – monitor LFTs.
- QT prolongation – monitor ECG and electrolytes.
- Bradycardia and rare cardiac events.
- Fatigue, headache, myalgia.
- Hyperglycemia in some patients.
Monitoring
- Liver function tests (AST, ALT, bilirubin) regularly.
- ECG and electrolytes for QT monitoring.
- Blood glucose in patients at risk.
- Signs of GI toxicity – supportive care, dose modification.
- CBC and renal function as clinically indicated.
Summary
Ceritinib (Zykadia®) is a second-generation ALK TKI used in ALK-positive NSCLC, including crizotinib-resistant cases. Key concerns are GI toxicity, hepatotoxicity, and QT prolongation, requiring careful monitoring and dose adjustment.