Entrectinib (Rozlytrek) is a targeted kinase inhibitor with significant efficacy in the treatment of ROS1‑positive non‑small cell lung cancer and NTRK fusion‑positive solid tumors, but it may also cause a variety of side effects.
I. Common and Serious Side Effects
1. Systemic Side Effects
(1) Most common (≥20%): fatigue, constipation, dysgeusia, edema, dizziness, diarrhea, nausea, paresthesia, dyspnea, myalgia, cognitive impairment, weight increased, cough, vomiting, pyrexia, arthralgia, vision blurred.
(2) Serious adverse reactions (incidence ≥2%): lung infection, dyspnea, fatigue, cognitive impairment, pulmonary embolism, hypoxia, pleural effusion, hypotension, diarrhea, urinary tract infection.
2. Cardiovascular Side Effects
(1) Congestive heart failure (3.4%): manifested as dyspnea, edema, persistent cough, shortness of breath on exertion.
(2) QT interval prolongation (3.1%): palpitations, dizziness, syncope may occur; severe cases can be life‑threatening.
(3) Myocarditis (0.3%): chest pain, palpitations, dyspnea may occur.
3. Central Nervous System Side Effects
(1) Cognitive impairment (27%): including confusion, decreased attention, memory impairment, aphasia, hallucinations, delirium.
(2) Mood disorders (10%): anxiety, depression, agitation; suicide cases have been reported.
(3) Dizziness (38%): may affect daily activities.
(4) Sleep disorders (14%): insomnia, somnolence, hypersomnia.
4. Musculoskeletal System
Increased fracture risk: 5% in adults and up to 25% in pediatric patients, mostly occurring in the lower extremities (femur, tibia), some without obvious trauma.
5. Hepatotoxicity
(1) Elevated AST (42%), elevated ALT (36%); Grade 3–4 incidence is approximately 2.5–2.8%.
(2) Median time to onset is 2 weeks.
6. Metabolic Abnormalities
(1) Hyperuricemia (9%), which may lead to gout and tumor lysis syndrome.
(2) Weight increased (39% in pediatric patients), some reaching Grade 3–4.
7. Ocular System
Vision impaired (21%): vision blurred (9%), photophobia (5%), diplopia (3.1%), photopsia, cataract, vitreous floaters.
8. Laboratory Abnormalities (≥20%)
(1) Anemia (67%), lymphopenia (40%), neutropenia (28%).
(2) Elevated creatinine, elevated uric acid, elevated transaminases, hypophosphatemia, hyperglycemia, etc.
II. Side Effect Mitigation and Management Strategies
1. Cardiovascular Management
(1) Pretreatment assessment: left ventricular ejection fraction should be measured in patients with symptoms or heart failure risk.
(2) Symptom monitoring: immediate medical attention for new or worsening dyspnea and edema.
(3) QT interval prolongation: regular ECG and electrolyte monitoring before and during treatment; avoid concomitant use with other QT‑prolonging drugs.
(4) Management: temporary interruption, dose reduction, or permanent discontinuation based on severity.
2. Central Nervous System Management
(1) Avoid hazardous activities: do not drive or operate machinery if dizziness, cognitive impairment, or blurred vision occurs.
(2) Mood monitoring: promptly inform a doctor if depression, anxiety, or hallucinations develop.
(3) Sleep management: maintain regular sleep schedule; adjust dosing time if necessary.
3. Fracture Risk Management
(1) Pediatric patients: fracture risk up to 25%; avoid high‑risk sports and seek medical care for pain or limited mobility.
(2) Adult patients: prevent falls and regularly assess bone health.
4. Hepatotoxicity Management
(1) Monitoring frequency: liver function tests every 2 weeks in the first month, then monthly.
(2) Management principle: temporary interruption, dose reduction, or permanent discontinuation based on transaminase elevation.
(3) Warning signs: immediate medical attention for decreased appetite, nausea, jaundice, or dark urine.
5. Hyperuricemia Management
(1) Regular monitoring: serum uric acid testing before and during treatment.
(2) Pharmacological treatment: urate‑lowering agents (e.g., allopurinol) may be initiated for symptomatic hyperuricemia.
(3) Temporary interruption for severe cases: consider resuming treatment after symptoms improve.
6. Ocular Management
(1) Regular ophthalmologic examinations: temporarily withhold treatment and refer to ophthalmology for new visual changes.
(2) Symptom reporting: promptly report diplopia, photophobia, blurred vision, etc.
7. Management of Weight Increased
(1) Regular weight monitoring: especially in pediatric patients.
(2) Diet and exercise: low‑calorie diet and moderate exercise to control weight gain.
III. Storage Conditions
1. Capsule Storage
(1) Temperature: 20°C to 25°C (68°F to 77°F); short‑term excursions permitted to 15–30°C.
(2) Moisture protection: store in original bottle with cap tightly closed.
(3) After reconstitution as oral suspension: use within 2 hours; do not store.
2. Oral Granules Storage
(1) Temperature: same as above, store at room temperature.
(2) Moisture protection: store in original packaging.
(3) Administration notes: sprinkle on soft food and take within 20 minutes; not for suspension or tube feeding.
