Table 5.

Management of regorafenib-related liver function abnormalities: dose-modification guidelines

Gradea	ALT and/or AST elevations	Occurrence	Recommended measures
≤Grade 2	≤5 × ULN	Any occurrence	• Continue treatment
			• Monitor liver function weekly until transaminases return to <3 × ULN (grade 1) or baseline
≥Grade 2 with concurrent bilirubin >2 × ULN	>3 × ULN	Any occurrenceb	• Discontinue treatment permanently
			• Monitor liver function weekly until resolution or return to baseline
Grade 3	>5 × to ≤20 × ULN	First occurrence	• Interrupt treatment
			• Monitor transaminases weekly until levels return to <3 × ULN or baseline
			• Patients may restart treatment if the potential risk outweighs the risk of liver toxicity
			• To restart treatment, reduce dose by 1 tablet (40 mg) and monitor liver function weekly for at least 4 weeks
		Recurrence	• Discontinue treatment permanently
Grade 4	>20 × ULN	Any occurrence	• Discontinue treatment permanently

Notes:

^aGrading by the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.03.2010)

^bexception: patients with Gilbert’s syndrome who develop elevated transaminases should be managed as per the outlined recommendations for the respective observed elevation of ALT and/or AST.

Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; ULN, upper limit of normal.