Table 2.
Mechanism and incidence of hypertension associated with cancer drug class and proposed treatment recommendation
| Cancer Drug Class | Mechanism of Hypertension | Incidence of Hypertension | Recommended Treatment |
|---|---|---|---|
| VEGF inhibitors | endothelial dysfunction, decrease in nitric oxide and prostacyclin I, increase in endothelin, vascular remodeling, capillary rarefaction, decreased renal excretion of sodium |
All Grade: 17–80% Grade 3–4: 6–9% |
CCB (e.g., amlodipine) ACEI (e.g., lisinopril) |
| TKI | decrease in NOS activity, activation of RAAS |
All Grade: 17–47% Grade 3–4: 4–6% |
ACEI CCB |
| Proteasome inhibitors | angiotensin-induced hypertension, aortic vascular remodeling | All Grade: 3–15% | ACEI or ARB (e.g., losartan) |
| Alkylating agents | oxidative damage to endothelial cells, increased intimal thickness, abnormal vascular remodeling, sodium retention | All Grade: 36–50% | ACEI or ARB |
| Steroids | promoting sodium and water retention, intrinsic vasoconstricting properties, enhanced sensitivity to endogenous vasopressors | All Grade: up to 13%a |
Diuretics (e.g., hydrochlorothiazide) Mineralocorticoid antagonists (e.g., spironolactone) |
| Calcineurin inhibitors and other immunosuppressive agents | sympathetic overactivity, increased renal sodium reabsorption (distal tubule ENaC activation), decrease in NO production, RAAS activation, altered renal PG synthesis | All Grade: 30–80% |
CCB Thiazide diuretics (especially for Tacrolimus) |
| Taxanes | endothelial dysfunction, enhanced toxicity of bevacizumab and anthracyclines | NA |
ACEI or ARB CCB |
| Abiraterone | increase in steroid precursors with mineralocorticoid properties (sodium and fluid retention) | NA |
Mineralocorticoid antagonists Diuretics |
| Recombinant human erythropoietin | increased blood viscosity, direct vasoconstricting properties, increased sensitivity to endogenous vasopressors | All Grade: 30–35% | CCB |
aData on the incidence of steroid-induced hypertension comes mainly from pediatric population treated for acute lymphocytic leukemia (ALL)
VEGF vascular endothelial growth factor, TKI tyrosine kinase inhibitor, NOS nitric oxide synthase, RAAS renin-angiotensin-aldosterone system, ENaC epithelial sodium channel, PG prostaglandin, CCB calcium channel blockers, ACEI angiotensin converting enzyme inhibitors, ARB angiotensin II receptor blocker, NA not available