Table A4.

Dose Modification or Delay for Nonhematologic Toxicities at Any Time^*

Toxicity Grade	Dose Interruption	Dose Modification	Dose for Subsequent Cycles
0-2	Treat on time	No change	No change
3	Delay until ≤ grade 1†	Reduce 1 dose level	If toxicity remains ≤ grade 1, dose re-escalation can be considered at discretion of treating investigator; if dose is re-escalated and toxicity (≥ grade 3) recurs, institute permanent dose reduction‡
4	Delay until ≤ grade 1†	Reduce by 1 dose level; permanent discontinuation can be considered at discretion of treating investigator‡

^*Except hand-foot-skin reaction, hypertension, and asymptomatic elevations in amylase/lipase and hypophosphatemia; excludes alopecia and nausea/vomiting/diarrhea/hypersensitivity unless persistent and/or recurrent despite optimal medical management.

^†If no recovery after a 4-week delay, study drug administration was permanently discontinued.

^‡Dose reductions below dose level − 3 were not allowed; if dose reductions below dose level − 3 were required, study drug administration was discontinued.