Table 2.

Recommended ixabepilone dose reductions and treatment discontinuations [10]

Issue	Recommendations
Monotherapy OR combination therapy dose modifications
Non-hematologic adverse events a
Grade 2 neuropathy lasting ≥7 days	Decrease dose by 20%
Grade 3 neuropathy lasting <7 days	Decrease dose by 20%
Grade 2 neuropathy lasting ≥7 days, or disabling neuropathy	Discontinue treatment
Any grade 3 toxicity other than neuropathy	Decrease dose by 20%
Transient grade 3 arthralgia/myalgia	No change in dose
Transient grade 3 fatigue	No change in dose
Grade 3 hand-foot syndrome	No change in dose
Any grade 4 toxicity	Discontinue treatment
Hematologic adverse events a
Neutrophils <500 cells/mm3 for ≥7 days	Decrease dose by 20%
Febrile neutropenia	Decrease dose by 20%
Platelets <25,000/mm3	Decrease dose by 20%
Platelets <50,000/mm3 with bleeding	Decrease dose by 20%
Potential drug interactions
Concomitant strong CYP3A4 inhibitor	Decrease dose to 20 mg/m2
Monotherapy dose modifications
Baseline hepatic impairment
AST and ALT ≤2.5 and bilirubin ≤1 × ULNb	No change in dose of monotherapy or combination therapy
AST and ALT ≤10 and bilirubin ≤1.5 × ULNb,c	Decrease monotherapy dose to 32 mg/m2
AST and ALT ≤10 and bilirubin >1.5–≤3 × ULNb,c	Decrease monotherapy dose to 20–30 mg/m2
Combination therapy dose modifications
Baseline hepatic impairment
AST or ALT >2.5 or bilirubin >1 × ULNb	Combination therapy is contraindicated

ALT alanine aminotransferase, AST aspartate aminotransferase, ULN upper limit of normal

^aToxicities graded in accordance with the National Cancer Institute (NCI) Common terminology criteria for adverse events (CTCAE v3.0)

^bExcludes patients whose total bilirubin is elevated due to Gilbert’s disease

^cApplies to ixabepilone monotherapy only. Ixabepilone and capecitabine combination therapy is contraindicated in this setting