Table 6.

Recommendations for the management of bevacizumab-associated toxicities.

Hypertension	Grade 1	Monitor weekly, continue bevacizumab
	Grade 2	Initiate antihypertensive therapy; hold bevacizumab if hypertension is symptomatic
	Grade 3	Escalate antihypertensive therapy (increase dose of single-agent or add agent); hold bevacizumab until hypertension is asymptomatic grade 2
	Grade 4	Permanently discontinue bevacizumab
Proteinuria	Grade 1	Monitor every 3 weeks, continue bevacizumab
	Grade 2
	Grade 3	Hold bevacizumab until proteinuria resolves to grade 2; consider angiotensin-converting enzyme inhibitor in consultation with internal medicine or nephrology
	Grade 4	Permanently discontinue bevacizumab
Gastrointestinal perforation		Maintain high index of suspicion when abdominal pain or obstructive symptoms occur; bowel rest and prompt evaluation with water-soluble contrast imaging. If patient has reasonable cancer prognosis and performance status, consider surgical repair. If prognosis and/or performance status are poor, risk of surgery might outweigh benefit. Manage coexisting abscess with systemic antibiotics±drainage (open or percutaneous). Permanently discontinue bevacizumab.
Arterial thromboembolism (transient ischemic attack, cerebrovascular infarction, unstable angina, troponin elevation, myocardial infarction)		Administer bevacizumab with caution in patient >65 years of age and/or with personal history of any arterial thromboembolism. Educate patients on warning signs and encourage prompt emergent care. Consult appropriate specialists (e.g., cardiology, neurology) to guide evaluation and management. Supportive care. Permanently discontinue bevacizumab.
Venous thromboembolism (deep vein thrombosis, pulmonary embolus)		Hold bevacizumab therapy until therapeutic anticoagulation established. Consider discontinuation of bevacizumab for complicated venous thromboembolism (failed adequate anticoagulation, respiratory compromise)
Reversible posterior leukoencephalopathy syndrome (RPLS)		Follow hypertension management suggestions. Maintain awareness of signs/symptoms of RPLS. Initiate prompt supportive care/management of hypertension. Permanently discontinue bevacizumab.
Wound-healing complications		Delay initiation of bevacizumab until 28 days following major surgery or until wound healing nearly complete. Delay major surgery, if possible, until 4 to 6 weeks following last dose of bevacizumab. Intravenous or intraperitoneal port placement and removal, endoscopic stenting, thoracentesis and paracentesis are not considered major procedures. Permanently discontinue bevacizumab in cases of fascial dehiscence.
Bleeding/hemorrhage		Use bevacizumab with caution in patients with vaginal and/or rectal metastases. Avoid bevacizumab use in patients with hemoptysis. Monitor minor bleeding (epistaxis, vaginal bleeding) with patient reporting, physical examination, and serial hemoglobin measurements. Permanently discontinue bevacizumab for bleeding events requiring acute transfusion resuscitation and/or interventional therapy (packing, surgery, embolization) to achieve hemostasis.