Anti-VEGF class toxicities (hypertension, proteinuria, bleeding, perforation)
The shared side effects of drugs that block blood vessel growth (bevacizumab, ramucirumab and VEGFR kinase inhibitors): high blood pressure, protein leaking into the urine, nosebleeds and more serious bleeding, slow wound healing, and rarely holes in the bowel.
VEGF maintains normal vessel integrity and healing, so blocking it raises blood pressure in 20-40% (treated with standard antihypertensives, a possible marker of efficacy), causes proteinuria, and impairs wound healing (bevacizumab is held for 4-6 weeks around surgery). Bleeding ranges from epistaxis to fatal haemoptysis in squamous lung cancer with central cavitating tumours (excluded from bevacizumab trials) and variceal bleeding in liver cancer (endoscopy required before atezolizumab-bevacizumab). Gastrointestinal perforation and fistula (1-2%, more after radiotherapy or with bowel involvement) and arterial thromboembolic events are the most serious. Multikinase inhibitors add hand-foot skin reaction, fatigue, diarrhoea and hypothyroidism.
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