• Wound-healing complications can occur with bevacizumab(Drug information on bevacizumab). Angiogenesis is very important in wound healing, and when inhibited, lack of angiogenesis can result in wound dehiscence and delayed wound healing, as well as fistula formation. In bevacizumab clinical trials, patients waited at least 28 days following surgery to begin the drug and the longest interval between the last dose of bevacizumab and wound dehiscence was 56 days. As bevacizumab has a long half-life of 20 days (range: 11–50 days) following surgery, bevacizumab should not be started until at least 28 days after major surgery, and the wound must be fully healed. Wound healing does not appear to be as significant a problem with sorafenib(Drug information on sorafenib) and sunitinib, probably because the drugs have such a short half-life compared to bevacizumab; this allows a more rapid recovery of normal wound healing processes. Patients should be taught the rationale for stopping the drug before surgery and not resuming it until the wound is fully healed. In addition, teach the patient to call the provider right away if a previous wound begins to drain or open.
• Proteinuria may occur. The glomeruli are made up of capillaries, and it appears that VEGF is necessary for glomerular endothelial repair; thus one hypothesis is that blocking VEGF may compromise the glomeruli endothelial cell integrity. The incidence is not actually known as most patients are asymptomatic, but in pivotal studies almost a third of patients had proteinuria. Assess urine for protein baseline, and regularly during treatment. If the urine dipstick is ≥ 2+, a 24-hour urine for protein should be collected prior to the next cycle, and if urine protein is ≥ 2g, delay bevacizumab dose until urine protein has fallen to < 2 g. In this case, repeat the 24-hour urine for protein prior to each cycle. If the 24-hour urinary protein falls to < 1 g, resume monitoring with urine dipstick.
• Arterial thromboembolism occurs in about 4.5% of patients, and complications include MI, CVA, and unstable angina. Risk factors include age > 65, pre-existing cardiac disease and previous history of thromboembolic events. Patients should be evaluated closely, and monitored during therapy. In some instances low dose aspirin(Drug information on aspirin) may be indicated.
• Cardiac abnormalities may be experienced. Left ventricular dysfunction may occur in approximately 11% of patients.[4,22] Assess baseline left ventricular ejection fraction (LVEF) for all patients, and continue to monitor during therapy if the patient has had a cardiac event within the preceding 12 months, such as myocardial angina or artery bypass graft, or has congestive heart failure. Interrupt or reduce dose in patients who have an LVEF < 50% and > 20% below baseline. QT prolongation may occur which increases the risk for ventricular arrythmias (eg, torsade de pointes), especially if the serum magnesium and potassium are low. Assess patient's history of QT prolongation, drug profile for drugs which may prolong the QT interval or antiarrythmic drugs, as well as serum electrolytes. If the patient is at risk, close monitoring with ECG and frequent electrolyte monitoring and repletion should be done.
• Laboratory abnormalities are a possibility. Assess complete blood count and platelet count and serum chemistries including phosphate at the beginning of each treatment cycle.
• Adrenal insufficiency has been found in lab animals. Monitor patient for adrenal insufficiency (muscle weakness, fatigue, weight loss, anorexia, hypotension, hypoglycemia, irritability, depression, salt craving) if the patient experiences surgery, trauma, or severe infection.
• Stomatitis may be encountered. Assess oral mucosa baseline and prior to each cycle. Teach patient oral hygiene regimen, and to report pain or difficulty chewing or swallowing. Management is similar to that for chemotherapy-induced oral stomatitis, and the drug dose may need to be interrupted or reduced.
• Skin alterations may occur. The skin may become yellow in 30% of patients. Depigmentation of the hair may occur when the patient is on therapy, becoming normal during the 2-week break, and then becoming depigmented again. This resembles a zebra-like hair color and will stop when the drug is stopped. Acral erythema, blistering, and desquamation may occur on the palms of the hands and soles of the feet. Teach patient to avoid repetitive pressure such as jogging, and to keep the surfaces of hands and feet moist with creams such as Eucerin or Udderly Smooth. Teach patient to report pain or interference with activities of daily living. Assess the impact on the patient's activities of daily living and comfort, and the need for drug interruption or dose reduction. Subungual splinter hemorrhage can occur under the fingernails. Dry skin can be managed with hydrating creams, and pruritis managed with anti-itch creams, or those that contain aloe vera. Scalp itch can be managed with antidandruff shampoos or tea tree oil.
• Hand-foot syndrome occurs in over a third of patients, and is usually grade 1/2; it appears during the first 6 weeks of treatment. Teach patients that this may occur, and to keep the skin of the hands and feet, as well as areas of friction, hydrated with skin emollients such as Eucerin cream, and to avoid repetitive movements such as jogging. Teach patients to assess skin areas, and to report skin erythema or edema that interferes with activities of daily living as this constitutes grade 2. Topical agents are used for up to 7 days but if there is no relief, the drug should be interrupted until it resolves to a grade 1, and then resumed at a reduced dose.
If grade 3 toxicity occurs, such as moist desquamation or ulceration so that the patient is unable to work or carry out activities of daily living, the drug should be interrupted until it resolves to grade 1/2. In addition, hyperkeratosis with callus formation may occur on the soles of the feet. Kerasal (over-the-counter) may reduce the callus formation, and wearing shock absorbers or gel shoe inserts may reduce discomfort.
• Cardiac ischemia or myocardial infarction occurs rarely, and the drug should be stopped or discontinued. Although rare, teach patients to report chest pain or shortness of breath right away.
• Laboratory abnormalities include hypophosphatemia, increased lipase and amylase, and less commonly, lymphopenia and thrombocytopenia. Teach patient that blood tests will be done frequently, and elevated lipase and amylase may require treatment.
• Sensory neuropathy may occur in 13% of patients compared to 6% in the control arm. Teach patients to report this if it occurs, and assess comfort and impact on activities of daily living.
This decade has seen the FDA approval of three antiangiogenic drugs. Although the drugs are in general well tolerated, significant and severe side effects are possible. The pathophysiology is still being determined for many of these, as well as optimal management. There are no prospective studies providing evidence for best practices, and so anecdotal and expert nursing experience guide us at this time. This is a perfect opportunity for oncology nurses to work together to conduct research and establish the evidence for best practice.