Incidence and management of ZIv-aflibercept related toxicities in colorectal cancer

Table 2 General guidelines for Ziv-aflibercept dosing and schedule modification due to adverse events per CTCAE 4.0

Event	Action to be taken
Hypertension
Grade 3	If not controlled with medication, discontinue Ziv
Grade 4	Discontinue Ziv
Proteinuria
> 2 g protein/24 h	Hold Ziv until proteinuria improves to < 2 g of protein/ 24 h
	Discontinue Ziv in a patient with > 2 g proteinuria/24 h that does not resolve in 3 mo time after holding Ziv. Work-up for proteinuria such as renal biopsy should be considered
grade 4 proteinuria (nephrotic syndrome)	Discontinue Ziv treatment
Gastrointestinal perforation
Gastrointestinal perforation or dehiscence	Discontinue Ziv
Thromboembolic events
Grade 3 venous thromboembolic event or incidentally discovered pulmonary embolus first occurrence	Hold Ziv treatment
	If the planned duration of therapeutic-dose anticoagulant therapy is £ 2 wk, Ziv should be held until the period of therapeutic-dose anticoagulant therapy is over
	If the planned duration of therapeutic-dose anticoagulant therapy is > 2 wk, Ziv should be held for 2 wk and then may be resumed during the period of therapeutic-dose anticoagulant therapy as soon as all of the following criteria are met: The patient must be on a stable dose of anticoagulant and, if on warfarin, have an INR within the target range (usually between 2 and 3) prior to restarting study drug treatment The patient has no history of Grade 3 or 4 hemorrhagic events before starting Ziv The patient has no evidence of tumor invading or abutting major blood vessels on any prior CT scan
Any grade arterial thromboembolic event or symptomatic Grade 4 venous thromboembolic event first occurrence	Discontinue Ziv
Hemorrhage
Grade 1 and 2	No dose modification
Grade 3 or 4 (first occurrence)	Discontinue study treatment