Fruquintinib capsules are a dedicated tumor angiogenesis inhibitor. They exert their effects mainly by blocking the VEGFR kinase family (three key targets: VEGFR 1, 2, and 3).
I. Pharmacological Effects
It effectively inhibits the proliferation of vascular endothelial cells, blocks neovascularization, cuts off the nutrient supply to tumors, and controls tumor growth. The specific mechanisms are as follows:
Directly reduces the activity of VEGFR kinases;
Prevents the intracellular phosphorylation of VEGFR 2/3 (a critical step in cell growth signal transduction);
Has been proven to significantly inhibit neovascularization by chick embryo chorioallantoic membrane assay and animal studies.
II. Indications
(I) Main Therapeutic Use
This product is indicated for the treatment of metastatic colorectal cancer (mCRC) in the following three patient populations:
Patients who have failed prior treatment with all three standard chemotherapy regimens: fluoropyrimidines, oxaliplatin, and irinotecan;
Patients who have received prior anti-vascular endothelial growth factor (anti-VEGF) therapy and require a treatment switch;
RAS wild-type patients confirmed by genetic testing who are unsuitable for or have not received anti-epidermal growth factor receptor (anti-EGFR) therapy.
(II) Symptomatic Relief
As monotherapy, this product can relieve the following symptoms caused by tumor progression in patients with metastatic colorectal cancer:
Recurrent diarrhea (markedly increased bowel movements, loose stools);
Persistent or paroxysmal abdominal pain.
It is especially suitable for patients with metastatic colorectal cancer who failed prior chemotherapy with fluoropyrimidines, oxaliplatin, irinotecan, and anti-VEGF/anti-EGFR therapy (RAS wild-type).
III. Specifications
Fruquintinib capsules are available in two strengths:
1 mg per capsule;
5 mg per capsul.
IV. Dosage and Administration
(I) Administration Method
May be taken with or without food; must be swallowed whole.
Use under the guidance of an experienced oncologist; do not self-medicate.
(II) Standard Dosage
5 mg (one 5 mg capsule) once daily.
Administer continuously for 3 weeks, followed by 1 week off treatment.
4 weeks constitute one full treatment cycle.
It is recommended to take at a fixed time each day.
If vomiting occurs after dosing, no supplemental dose is needed.
If a dose is missed, do not double the next dose; resume the regular dosing schedule as planned.
(III) Dose Adjustment Principles
Dose modification (temporary interruption, dose reduction, permanent discontinuation) will be made by the physician based on the patient’s response, following the principle of interruption first, then gradual reduction:
If adverse reactions improve to Grade 1 or lower within 1 week after interruption, the original dose may be resumed;
If recovery occurs within 2 weeks:
First dose reduction: 4 mg once daily (four 1 mg capsules);
Second dose reduction: 3 mg once daily (three 1 mg capsules);
If intolerance persists at 3 mg daily, permanent discontinuation is required.
(IV) Dose Adjustment for Specific Adverse Reactions
Treatment interruption required
Grade 2 bleeding; recurrent Grade 2 oral ulcers; painful hand-foot redness/swelling affecting daily activities; 24-hour urinary protein > 2 g; platelet count (50–75) ×10⁹/L; and all Grade 3–4 adverse reactions (except those requiring permanent discontinuation).
Dose reduction required
Adverse reactions improve to Grade 1 or lower within 2 weeks of treatment interruption.
Permanent discontinuation required
Severe bleeding (Grade 3 or higher), gastrointestinal perforation, wound dehiscence requiring intervention, organ fistula, nephrotic syndrome, hypertensive crisis, severe liver injury (transaminases > 20 × upper limit of normal), intolerance at the lowest dose, failure to recover within 2 weeks of interruption.
Adjustment for hand-foot skin reaction (HFSR)
Grade 1 (numbness, dysesthesia, painless swelling, erythema; no impact on daily activities): Maintain dose, provide supportive care.
Grade 2 (painful erythema/swelling; affects daily activities): Interrupt treatment. If recovery to Grade 1 or lower within 2 weeks, maintain original dose or reduce by one level.
Grade 3 (wet desquamation, ulceration, blistering; severely impairs daily life):
First occurrence: reduce to 4 mg daily;
Second occurrence: reduce to 3 mg daily;
Third occurrence: permanently discontinue if still intolerant.
V. Adverse Reactions
(I) Common Adverse Reactions
Hypertension, proteinuria, hand-foot skin reaction, abnormal bleeding, hoarseness, elevated transaminases, abdominal discomfort, elevated bilirubin, thyroid dysfunction, infection, diarrhea, fatigue, decreased appetite, oral mucositis, weight loss, positive fecal occult blood, thrombocytopenia.
(II) Serious Adverse Reactions
Major bleeding, severe liver function abnormality, severe pulmonary infection, hypertensive crisis.
Patients should contact a physician immediately if any of the above symptoms occur; vital sign monitoring may be necessary.
VI. Contraindications
The following populations are contraindicated:
Patients with hypersensitivity to the active ingredient or any excipients of this product;
Patients with uncontrolled severe bleeding;
Patients with active gastric ulcer or unhealed intestinal ulcer;
Patients with unhealed gastrointestinal perforation;
Patients with gastrointestinal or other organ fistulas;
Patients with severe hepatic or renal failure;
Pregnant or lactating women.
VII. Precautions
Contraception
Female patients: effective contraception required during treatment and for 1 month after stopping.
Male patients: effective contraception required during treatment and for 3 months after stopping.
Pre-treatment disclosure
Patients taking other medications or with chronic diseases must fully inform their physician of their health status and medication history before use.
Cautionary use
Patients at high risk of bleeding (within 1 month after major surgery, coagulation indices > 1.5 × upper limit of normal); history of arterial thrombosis/cerebral infarction; moderate to severe hepatic or renal impairment; elderly patients.
No safety data in adolescents under 18 years old; use not recommended.
Treatment monitoring
Liver function: monitor and perform regular tests in patients with mild to moderate hepatic impairment;
Renal function: monitor urinary protein; intensified monitoring for creatinine clearance < 50 mL/min;
Coagulation: regular blood routine and coagulation tests; increased monitoring frequency if anticoagulants are co-administered;
Blood pressure: control BP < 140/90 mmHg before treatment; weekly monitoring at initiation, then per cycle;
Urine: regular urinary protein testing; intensified monitoring in patients with renal impairment.
Immediate discontinuation
Permanent discontinuation and emergency treatment are required for severe bleeding, gastrointestinal perforation, arterial thrombosis/stroke, reversible posterior leukoencephalopathy syndrome (RPLS).
Temporarily interrupt treatment before major surgery; resume only after full wound healing.
Temporarily interrupt for Grade 3 or higher severe infection until infection is controlled.
Instructions may vary between manufacturers. Consult a physician or pharmacist in case of conflict.
VIII. Drug Interactions
This product may affect P-gp and BCRP transporters in vivo. Concomitant use with drugs dependent on these transporters (certain anticancer agents, immunosuppressants) may increase their efficacy or adverse reactions.
Inform the physician of all concomitant medications before combination therapy, monitor for abnormal reactions during treatment, and the physician may adjust doses accordingly.
IX. Use in Specific Populations
Pregnancy: Contraindicated.
Lactation: Contraindicated.
Children/adolescents: No clinical data; use not recommended.
Elderly: Use cautiously under medical supervision; generally no initial dose adjustment needed.
Individuals planning pregnancy: Effective contraception required before, during, and after treatment.
X. Overdosage
The specific hazards of overdose are not yet clear. No specific antidote is available.
If overdose is suspected, discontinue treatment immediately, monitor the patient continuously, and provide supportive symptomatic treatment.
XI. Missed Dose
If a dose is occasionally missed, do not make up for the missed dose or double the next dose. Continue with the next scheduled dose as normal.
XII. Post-Administration Information
Driving and operating machinery
If dizziness, fatigue, or other symptoms affecting concentration occur, avoid driving or operating heavy machinery until symptoms resolve completely.
Storage
Seal and store in a cool place below 30 °C.
Discontinue use if the product shows abnormalities such as discoloration or caking.
Keep all medicines out of the reach of children.
