Table 2.

Dose modifications for non-hematological toxicities other than asthenia and grade 3 anorexia.

Worst toxicity by CTCAE grade	Nal-IRI	5-FU	Oxaliplatin
Grade 1 or 2, including diarrhea	100% of previous dose	100% of previous dose, except for grade 2 hand foot syndrome, grade 2 cardiac toxicity, or any grade neurocerebellar toxicity	100% of previous dose
Grade 3 or 4, including diarrhea (except nausea and vomiting)	1st occurrence: reduce dose to 40 mg/m2 2nd occurrence: reduce dose to 30 mg/m2	1st occurrence: reduce dose by 25% 2nd occurrence: reduce dose another 25% (50% of original dose)* except for grade 3 or 4 hand foot syndrome	1st occurrence: 100% of previous dose 2nd occurrence: reduce dose to 50 mg/m2
Grade 3 or 4 nausea and/or vomiting despite antiemetic therapy	Optimize antiemetic therapy AND reduce dose to 40 mg/m2; if the patient is already receiving 50 mg/m2, reduce dose to 40 mg/m2	Optimize antiemetic therapy AND reduce dose by 25%; if the patient is already receiving a reduced dose, reduce dose an additional 25%f	1st occurrence; 100% of previous dose 2nd occurrence: reduce dose to 50 mg/m2
Grade 2 hand foot syndrome	100% of previous dose	1st occurrence: reduce dose by 25% 2nd occurrence: reduce dose another 25% (50% of original dose)	100% of previous dose
Grade 3 or 4 hand foot syndrome	1st occurrence: reduce dose to 40 mg/m2 2nd occurrence: reduce dose to 30 mg/m2	Discontinue therapy	No dose modifications required
Any grade neurocerebellar or >grade 2 cardiac toxicity	No dose modifications required	Discontinue therapy	No dose modifications required
Sensory neuropathy	No dose modifications required	No dose modifications required	Grade 2, persistent: reduce dose to 50 mg/m2 Grade 3: recovers prior to next cycle and reduce dose to 50 mg/m2 Grade 3, persistent: discontinue therapy Grade 4: discontinue therapy

CTCAE, common toxicities adverse events criteria; 5-FU, 5-fluorouracil; Nal-IRI, nanoliposomal irinotecan.