Crizotinib
XALKORI
What it isALK and ROS1 tyrosine kinase inhibitor; ALK- or ROS1-positive lung cancer.
Why this oneIt was the first ALK inhibitor and remains an option in ROS1 disease.
What limits itPoor CNS penetration, so brain relapse is common and later agents replaced it. Visual disturbance, edema and hepatotoxicity.
FDA-approved for
- ALK- or ROS1-positive non-small cell lung cancer (2011)
FDA label
Read the full label on DailyMed ↗
| FDA dosing | Population | Start | Target | Max |
|---|---|---|---|---|
| ALK- or ROS1-positive metastatic NSCLC | Adults | 250 mg BID | 250 mg BID | 250 mg BID |
| Relapsed/refractory systemic ALK-positive ALCL | Pediatric patients & young adults | 280 mg/m² BID | 280 mg/m² BID | 280 mg/m² BID |
| Unresectable/recurrent/refractory ALK-positive IMT | Adults | 250 mg BID | 250 mg BID | 250 mg BID |
| Unresectable/recurrent/refractory ALK-positive IMT | Pediatric patients | 280 mg/m² BID | 280 mg/m² BID | 280 mg/m² BID |
Renal Severe renal impairment: reduce dose (see label section 2.8)
Hepatic Moderate or severe hepatic impairment: reduce dose (see label section 2.7)
Instructions
- Select patients by ALK or ROS1 positivity in tumor specimens
- Monitor LFTs every 2 weeks for first 2 months then monthly; monitor CBC weekly for first month then monthly
- Obtain baseline and follow-up ophthalmologic/retinal exams in pediatric ALCL/IMT within 1 month then every 3 months
Cautions
- Hepatotoxicity, including fatal — monitor with periodic liver testing
- Interstitial lung disease/pneumonitis — permanently discontinue
- QT interval prolongation — monitor ECG and electrolytes
- Bradycardia — monitor heart rate and blood pressure
- Severe visual loss — discontinue if it occurs
- GI toxicity (nausea, vomiting, diarrhea, stomatitis) in pediatric/young adult ALCL and pediatric IMT
- Embryo-fetal toxicity
Adverse reactions
- Vision disorders
- Nausea, diarrhea, vomiting, constipation
- Edema
- Elevated transaminases
- Fatigue, decreased appetite, dizziness, neuropathy
- (ALCL) neutropenia, lymphopenia, thrombocytopenia
Pregnancy Can cause fetal harm; embryotoxicity/fetotoxicity in animals; advise effective contraception
Lactation No data; advise not to breastfeed during treatment and for 45 days after last dose
NO BOXED WARNINGS
Principal riskPoor CNS penetration, so brain relapse is common
Cost, est. cash$5,000–$30,000+/month or cycle
Generic entry2029 est.
Classes and tags
Clinical profile
Legacy pregnancy categoryD
Defining liabilityMyelosuppression and agent-specific hepatic, cardiac, pulmonary, neurologic or reproductive toxicity require oncology monitoring.
Mechanism of action: Crizotinib ballicule
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