Active Ingredient: Regorafenib
Regorafenib is indicated as monotherapy for the treatment of adult patients with unresectable or metastatic gastrointestinal stromal tumours (GIST) who progressed on or are intolerant to prior treatment with imatinib and sunitinib.
For this indication, competent medicine agencies globally authorize below treatments:
Oral
160 - 160 mg
From 160 To 160 mg once every day for 21 day(s)
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 ≥2.
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 grade | Occurrence | Recommended dose modification and measures |
|---|---|---|
| Grade 1 | Any | Maintain dose level and immediately institute supportive measures for symptomatic relief. |
| Grade 2 | 1st occurrence | Decrease 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 occurrence | Interrupt 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 occurrence | Interrupt 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 occurrence | Discontinue treatment with regorafenib permanently. | |
| Grade 3 | 1st occurrence | Institute 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 occurrence | Institute 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 occurrence | Discontinue 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 AST | Occurrence | Recommended measures and dose modification |
|---|---|---|
| ≤5 times upper limit of normal (ULN) (maximum Grade 2) | Any occurrence | Continue regorafenib treatment. Monitor liver function weekly until transaminases return to <3 times ULN (Grade 1) or baseline. |
| >5 times ULN ≤20 times ULN (Grade 3) | 1st occurrence | Interrupt 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-occurrence | Discontinue treatment with regorafenib permanently. | |
| >20 times ULN (Grade 4) | Any occurrence | Discontinue treatment with regorafenib permanently. |
| >3 times ULN (Grade 2 or higher) with concurrent bilirubin >2 times ULN | Any occurrence | Discontinue treatment with regorafenib permanently. Monitor liver function weekly until resolution or return to baseline. Exception: patients with Gilbert’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. |
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.
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