If a patient experienced any grade 2 toxicity and the toxicity was considered to be mainly due to capecitabine treatment, drug administration was withheld until the grade 2 toxicity resolved to grade 0 1 before being restarted at the same dose with prophylactic treatment (for nausea, diarrhoea, hand foot syndrome) where necessary and possible.
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Up until 80 mg m−2, grade 2 toxicity was not observed during the first course.
Patients should have symptomatic treatment as indicated for grades 1 and 2, with regorafenib treatment interrupted for a minimum of 7 days (maximum 28 days) until the HFSR reaches grade 1 or 0; regorafenib should then be resumed at one dose level lower than the previous dose (see Table 4).
Any recurrent varices should be treated with further VBL until eradication (level 1b, grade B).
It is suggested that varices are banded at 2 4-weekly intervals until eradication (level 1b, grade B).
If necessary, the regorafenib dose can be reduced by one level for a minimum of 7 days (maximum 28 days), until the HFSR reaches grade 1 or 0, at which point patients can resume treatment at the full starting dose.
If grade 3 haematological toxicity was recorded, the treatment was withheld until the recovery grade ⩽2 or blood counts had returned to baseline after which sunitinib was resumed at the same dose level.
For grade 3 the recommendation is provide treatment as indicated for grades 1 and 2 and to include the following: Discontinue the Sorafenib for a minimum of 7 days until the HFS reaches grade 1 or 0, and then resume treatment at 50% of the full dose [ 18].
No specific management recommendations regarding hepatic toxicity are made for dasatinib, but the general recommendation for any grade 2/3 nonhematologic AE not responsive to symptomatic measures is to treat it as grade 4 and interrupt treatment until the grade is 1 or lower.
