VEGFI-induced Hypertension: How to Manage This New Syndrome?

Malignant tumors require a generous blood supply to remain viable. A novel and effective class of chemotherapy agents interfere with a tumor’s ability to attract a blood supply for nutrition and growth. The he drugs are referred to as “VEGFIs” or vascular endothelial growth factor inhibitors (bevacizumab is the one most widely used). The drugs’ mechanism of action is mediated through tyrosine kinase and their interference inhibits tumor vasodilatation, cell proliferation, and differentiation into blood vessels.¹

Although the VEGFIs have become successful adjuncts in the treatment of cancer, up to 80% of individuals who are treated with drugs in this class develop elevated blood pressures and even hypertensive crises.¹  Hypertension has been noticed in every trial in which VEGFIs have been used.¹

Currently, the mechanism underlying VEGFI-induced hypertension is unknown. Nitric oxide down-regulation at the endothelial level may be the culprit, but all the answers are not in. Nonetheless, non-oncology physicians will be seeing patients with hypertension as a consequence of VEGFIs utilized as treatment for various cancers and should be informed regarding specifics of diagnosis and treatment options.

See what you do and/or don’t know about this side effect.

1. Which of the following statements is/are correct:

A. Hypertension as a consequence of VEGFI therapy occurs after repeated, long-term administration.

B. VEGFI-induced hypertension does not resolve after treatment is completed.

C. Only dihydropyridine calcium channel blockers are effective in lowering blood pressures in patients being treated with a VEGFI.

D. VEGFIs have a greater effect on diastolic than on systolic blood pressures.

Please click here for answer and discussion. 

The correct answer is: None of the statements are correct.^1-3

Hypertension with VEGFI use occurs very early, usually with the first cycle of treatment and within hours to days of VEGFI initiation.¹ It typically completely resolves after therapy has ended.¹ Although data are not robust, no antihypertensive agents are more or less effective to treat hypertension associated with VEGFI therapy. Some studies favor dihydropyridine calcium channel blockers, others have had success with ACEIs or ARBS.^1,2 VEGFIs tend to elevate systolic more than diastolic blood pressures.¹

2. VEGFIs are approved to treat which of the following malignancies?

A. Colorectal cancer

B. Renal cell carcinoma

C. Non-small cell lung cancer

D. Glioblastoma

E. Gynecologic malignancies such as ovarian and cervical cancers.

Please click here for answer and discussion.

The correct answer is: VEGFIs are approved to treat all of the malignancies listed above.³

Since there are many questions remaining to answer in the context of VEGFI-induced hypertension, are there any recommendations for the non-oncologist? At this juncture, it would be reasonable to consider the following:

• When VEGFIs are indicated, see the patient at baseline.

• If a patient is already being treated for hypertension, ensure that they are at target and “get a handle” on all other cardiovascular risk factors.

• If a patient does not have hypertension when VEGFI therpay begins, plan to see them more frequently early in the course of treatment, when they are most likely to manifest hypertension.

Treat patients with VEGFI-related hypertension as you would any patient with hypertension as there are no hard and fast rules for choice of therapy at this time. It seems commonly prescribed medications include ACEIs or ARBS in combination with dihydropyridine calcium channel blockers. If a hypertensive crisis occurs consult colleagues who are comfortable with that entity.

References

1. Small HY, Montezano AC, Rios FJ, et al. Hypertension due to antiangiogenic cancer therapy with vascular endothelial growth factor inhibitors: understanding and managing a new syndrome. Can J Cardiol. 2014; 30:534-543.
2. Derosa GG, Izzedine H, Albiges I, Escudier B. Hypertension and angiotensin system inhibitors in patients with metastatic renal cell carcinoma. Oncol. Rev. 2016; 10:54-58.
3. Corr BR, Breed C, Sheeder J, et al. Bevacizumab induced hypertension in gynecologic cancer: Does it resolve after completion of therapy? Gynecologic Oncology Rep. 2016; 17: 65-68.