Hepatocellular carcinoma (HCC)

Active Ingredient: Regorafenib

Indication for Regorafenib

Population group: only adults (18 years old or older)

Regorafenib is indicated as monotherapy for the treatment of adult patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib.

For this indication, competent medicine agencies globally authorize below treatments:

160 mg once daily

Route of admnistration

Oral

Defined daily dose

160 - 160 mg

Dosage regimen

From 160 To 160 mg once every day for 21 day(s)

Detailed description

The recommended dose of regorafenib is 160 mg taken once daily for 3 weeks followed by 1 week off therapy. This 4-week period is considered a treatment cycle.

If a dose is missed, then it should be taken on the same day as soon as the patient remembers. The patient should not take two doses on the same day to make up for a missed dose. In case of vomiting after regorafenib administration, the patient should not take additional tablets.

Treatment should continue as long as benefit is observed or until unacceptable toxicity occurs.

Patients with performance status (PS) 2 or higher were excluded from clinical studies. There is limited data in patients with PS โ‰ฅ2.

Posology adjustments

Dose interruptions and/or dose reductions may be required based on individual safety and tolerability. Dose modifications are to be applied in 40 mg steps. The lowest recommended daily dose is 80 mg. The maximum daily dose is 160 mg.

For recommended dose modifications and measures in case of hand-foot skin reaction (HFSR)/palmar-plantar erythrodysesthesia syndrome see Table 1.

Table 1. Recommended dose modifications and measures for HFSR:

Skin toxicity gradeOccurrenceRecommended dose modification and measures
Grade 1AnyMaintain dose level and immediately institute supportive measures for symptomatic relief.
Grade 21st occurrenceDecrease dose by 40 mg and immediately institute supportive measures. If no improvement occurs despite dose reduction, interrupt therapy for a minimum of 7 days, until toxicity resolves to Grade 0-1. A dose re-escalation is permitted at the discretion of the physician.
No improvement within 7 days or 2nd occurrenceInterrupt therapy until toxicity resolves to Grade 0-1. When re-starting treatment, decrease dose by 40 mg. A dose re-escalation is permitted at the discretion of the physician.
3rd occurrenceInterrupt therapy until toxicity resolves to Grade 0-1. When re-starting treatment, decrease dose by 40 mg. A dose re-escalation is permitted at the discretion of the physician.
4th occurrenceDiscontinue treatment with regorafenib permanently.
Grade 31st occurrenceInstitute supportive measures immediately. Interrupt therapy for a minimum of 7 days until toxicity resolves to Grade 0-1. When re-starting treatment, decrease dose by 40 mg. A dose re-escalation is permitted at the discretion of the physician.
2nd occurrenceInstitute supportive measures immediately. Interrupt therapy for a minimum of 7 days until toxicity resolves to Grade 0-1. When re-starting treatment, decrease dose by 40 mg.
3rd occurrenceDiscontinue treatment with regorafenib permanently.

For recommended measures and dose modifications in case of worsening of liver function tests considered related to treatment with regorafenib see Table 2.

Table 2. Recommended measures and dose modifications in case of drug-related liver function test abnormalities:

Observed elevations of ALT and/or ASTOccurrenceRecommended measures and dose modification
โ‰ค5 times upper limit of normal (ULN) (maximum Grade 2)Any occurrenceContinue regorafenib treatment. Monitor liver function weekly until transaminases return to <3 times ULN (Grade 1) or baseline.
>5 times ULN โ‰ค20 times ULN (Grade 3)1st occurrenceInterrupt regorafenib treatment. Monitor transaminases weekly until return to <3 times ULN or baseline. Restart: If the potential benefit outweighs the risk of hepatotoxicity, re-start regorafenib treatment, reduce dose by 40 mg (one tablet), and monitor liver function weekly for at least 4 weeks.
Re-occurrenceDiscontinue treatment with regorafenib permanently.
>20 times ULN (Grade 4)Any occurrenceDiscontinue treatment with regorafenib permanently.
>3 times ULN (Grade 2 or higher) with concurrent bilirubin >2 times ULNAny occurrenceDiscontinue treatment with regorafenib permanently. Monitor liver function weekly until resolution or return to baseline. Exception: patients with Gilbertโ€™s syndrome who develop elevated transaminases should be managed as per the above outlined recommendations for the respective observed elevation of ALT and/or AST.

Dosage considerations

Regorafenib should be taken at the same time each day. The tablets should be swallowed whole with water after a light meal that contains less than 30% fat.

Active ingredient

Regorafenib

Regorafenib is an oral tumour deactivation agent that potently blocks multiple protein kinases, including kinases involved in tumour angiogenesis (VEGFR1, -2, -3, TIE2), oncogenesis (KIT, RET, RAF-1, BRAF, BRAFV600E), metastasis (VEGFR3, PDGFR, FGFR) and tumour immunity (CSF1R). Regorafenib inhibits mutated KIT, a major oncogenic driver in gastrointestinal stromal tumours, and thereby blocks tumour cell proliferation.

Read more about Regorafenib

Related medicines

Develop a tailored medication plan for your case, considering factors such as age, gender, and health history

Ask the Reasoner

Liability Disclaimer : RxReasoner has utilized reasonable care in providing content and services that are accurate, complete and up to date. However, RxReasoner does not accept any responsibility or liability about it. The content and services of RxReasoner are for informational purposes only and they are not intended to be a substitute for the knowledge, expertise, skill, and judgment of physicians, pharmacists, nurses, or other healthcare professionals involved in patient care. RxReasoner offers no medical advice. Users are responsible for the use of the provided content. A shown indication or treatment should not be construed to indicate that the medication is safe, appropriate, or effective in any given patient or under any particular circumstances. The absence of an indication or treatment should not roule out the existence of other appropriate medications. Always seek the advice of a physician or other qualified health provider with any questions you may have regarding a medical condition or medicament. RxReasoner is not liable for any damages allegedly sustained arising out of the use of its content and services.