TABLE III.

Dose modifications for crizotinib related adverse events¹⁶

Toxicity	ctcae grade	Toxicity description	Dosing
Hematologic toxicity
	Grade 3	anc: <1.0 to 0.5×109/L Platelets: <50.0 to 25.0×109/L	Withhold until recovery to grade 2 or lower. Resume at same dose schedule.
	Grade 4	anc: <0.5×109/L Platelets: <25.0×109/L	Withhold until recovery to grade 2 or lower. Resume at 200 mg twice dailya.
Hepatotoxicity
	Grade 3 or 4 alt or ast elevation and Grade 1 or lower total bilirubin	ast and alt Grade 2: >3.0 to 5.0×uln Grade 3: >5.0 to 20.0×uln Grade 4: >20.0×uln	Withhold until recovery to grade 1 or lower. Resume at 200 mg twice dailyb.
	Grade 2, 3, or 4 alt or ast elevation and concurrent grade 2, 3, or 4 total bilirubin elevationc	Bilirubin Grade 2: >1.5 to 3.0×uln Grade 3: >3.0 to 10.0×uln Grade 4: >10.0×uln	Permanently discontinue.
Pneumonitis
	Any graded		Permanently discontinue.
QTc prolongation
	Grade 3e	QTc ≥ 500 ms	Withhold until recovery to baseline or to a QTc ≤ 480 ms Resume at 200 mg twice dailyb,f
	Grade 4	QTc ≥ 500 ms and life-threatening signs or symptoms	Permanently discontinue.

^aIn case of recurrence, hold until recovery to grade 2 or lower, and then resume at 250 mg daily. Permanently discontinue in case of further grade 4 recurrence.

^bIn case of recurrence, hold until recovery to grade 1 or lower, and then resume at 250 mg daily. Permanently discontinue in case of further grade 3 or 4 recurrence.

^cIn the absence of cholestasis or hemolysis.

^dIn the absence of disease progression, other pulmonary disease, infection, or radiation effect.

^eOn at least 2 separate electrocardiograms.

^fEnsure that hypokalemia, hypomagnesemia, and hypocalcemia are corrected.

ctcae = U.S. National Cancer Institute Common Terminology Criteria for Adverse Events; anc = absolute neutrophil count; ast = aspartate aminotransferase; alt = alanine aminotransferase; uln = upper limit of normal.