Boratinib is a targeted drug used to treat non-small cell lung cancer. Its standard dose is 100mg orally per day, and the dose needs to be adjusted according to adverse reactions or special population conditions. The resistance mechanism is mainly related to ALK gene mutations, and attention should be paid to multiple medication risks such as central nervous system effects and hyperlipidemia.

1. Usage and dosage

The standard dose is 100mg orally once daily, and treatment is continued until disease progression or intolerable toxicity occurs. If there is less than 4 hours before the next administration when missing medication, it should be skipped and double supplementation is prohibited. For patients with severe renal dysfunction, the dosage should be reduced to 75mg/day. For patients with mild liver dysfunction, no adjustment is needed, and there is insufficient data for moderate to severe cases.

(1) Principle of dose adjustment

Reduce to 75mg/day for the first dose and 50mg/day for the second dose. Unable to tolerate 50mg, permanent discontinuation of medication is required. The central nervous system level 1 response can maintain the original dose, levels 2-3 require a pause and reduction, and level 4 requires permanent discontinuation of medication.

2 Resistance mechanisms

Mainly due to secondary mutations in the ALK kinase domain (such as G1202R), drug binding affinity decreases. Other mechanisms include activation of bypass signals (such as EGFR pathway) or pharmacokinetic changes (such as decreased blood-brain barrier penetration efficiency). The type of drug-resistant mutation needs to be confirmed through genetic testing.

3 Precautions

(1) Central nervous system impact

May cause epilepsy, cognitive impairment, or emotional abnormalities, with a median onset time of 1.4 months. Most symptoms can be relieved by adjusting the dosage, and close monitoring of neurological and psychiatric symptoms is necessary.

(2) Cardiovascular risk

May cause prolonged PR interval or atrioventricular block. Second degree blockade requires a pause until PR<200ms before reducing dosage, while third degree blockade requires the installation of a pacemaker or permanent discontinuation of medication.

(3) Metabolic abnormalities

Hyperlipidemia requires regular monitoring of blood lipids, and medication should be suspended at level 4. Hypertension grade 3 should be temporarily suspended until grade 1, and the original dose should be continued. If there is a recurrence, the dosage should be reduced. High blood sugar levels 3-4 require a pause and optimization of the glycemic control plan.

(4) Special populations

Pregnant women are prohibited from taking medication, and breastfeeding is prohibited within 7 days of discontinuation. Women of childbearing age should use non hormonal contraception for 6 months after discontinuation, while men should use contraception for 3 months after discontinuation. Elderly patients do not require special adjustments.