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Silk et al. Hepatoma Res 2020;6:73 I http://dx.doi.org/10.20517/2394-5079.2020.61 Page 11 of 16

III: Macules/papules 1st occurrence: Interrupt Proceed the same as for grade II toxicity 1st occurrence: Interrupt
covering > 30% BSA treatment until toxicity treatment and start
with moderate or severe resolves to Grade supportive measures.
symptoms; limiting self 0-1. When resuming Interrupt until toxicity
care ADL treatment, decrease dose resolves or improves to
by one dose level (400 grade 1. But treatment
mg daily or 400 mg every must be stopped for
other day) a minimum of 7 days.
2nd occurrence: Interrupt Resume dose at 120 mg
treatment until toxicity daily
resolves to Grade 2nd occurrence: Interrupt
0-1. When resuming treatment and start
treatment, decrease dose supportive measures.
by one dose level (400 Interrupted until toxicity
mg daily or 400 mg every resolves or improves
other day) to grade 1. Stop for a
3rd occurrence: minimum of 7 days.
Discontinue Resume dose at 80 mg
daily
3rd occurrence:
Discontinue

Table 3. Stomatitis and tyrosine kinase inhibitor treatment modifications
Stomatitis Tyrosine kinase inhibitor
Grade Sorafenib Lenvatinib Cabozantinib Regorafenib
I: asymptomatic or mild No modification, use topical relief agents
symptoms
II: moderate pain or 1st occurrence: Continue 1st occurrence: withhold 1st occurrence: withhold 1st occurence: Reduce
ulcers that do not treatment and consider until improves to Grade until improves to Grade 1 dose to 120 mg daily and
interfere with oral intake topical therapy for 0-1 or baseline. Resume at or baseline. Resume at 40 start supportive therapy.
symptomatic relief. If no 8 mg if ≥ 60 kg, 4 mg if < mg daily If the toxicity does not
improvement within 7 60 kg 2nd occurrence: Withhold improve within 7 days
days, see below 2nd occurrence: withhold until improves to Grade 1 interrupt therapy until
No improvement, 2nd until improves to Grade or baseline. Resume at 20 the toxicity resolves or
or 3rd occurrence: 0-1 or baseline. Resume mg daily improves to grade 1. Then
Interrupt treatment until at 4 mg if ≥ 60 kg, 4 mg 3rd occurrence: withhold can restart at 120 mg daily
toxicity resolves to Grade Q.O.D. if < 60 kg until improves to Grade 2nd occurrence: Interrupt
0-1. When resuming 3rd occurrence: Withhold 1 or baseline. Resume at and institute supportive
treatment, decrease dose until improves to Grade 20 mg daily if tolerated or measures until toxicity
by one dose level (400 0-1 or baseline. Resume discontinue resolves or improves to
mg daily or 400 mg every at 4 mg Q.O.D if ≥ 60 kg, grade 1. Reduce dose to 80
other day) discontinue < 60 kg mg daily
4th occurrence: 3rd occurrence:
Discontinue Discontinue if failure to
tolerate 80 mg daily dose
III: Severe pain 1st occurrence: Interrupt Proceed the same as for grade II toxicity 1st occurrence: Interrupt
interfering with oral treatment until toxicity treatment and start
intake resolves to Grade supportive measures.
0-1. When resuming Treatment must be
treatment, decrease dose interrupted until toxicity
by one dose level (400 resolves or improves to
mg daily or 400 mg every grade 1. But treatment
other day) must be stopped for
2nd occurrence: Interrupt a minimum of 7 days.
treatment until toxicity Resume dose at 120 mg
resolves to Grade daily
0-1. When resuming 2nd occurrence: Interrupt
treatment, decrease dose treatment and start
by one dose level (400 supportive measures.
mg daily or 400 mg every Treatment must be
other day) interrupted until toxicity
3rd occurrence: resolves or improves to
Discontinue grade 1. But treatment
must be stopped for
a minimum of 7 days.
Resume dose at 80 mg
daily
3rd occurrence:
Discontinue