According to a retrospective study, the use of angiotensin system inhibitors (ASIs), such as lisinopril, captopril, and losartan, improved the survival of patients with metastatic renal cell carcinoma (RCC) by nine months, compared with patients who were not receiving these types of agents. Survival was even higher in patients receiving ASIs along with treatment targeting the VEGF pathway. Hypertension is a common condition in the United States, and this is the largest analysis to date evaluating the role of ASIs on outcomes in patients with cancer.
“Though larger prospective studies are needed, based on the results of this study, an ASI should be considered for patients with metastatic renal cell carcinoma who need an antihypertensive and do not have any contraindications that preclude their use, especially in patients receiving VEGF targeted treatments,” said lead author Rana McKay, MD, a clinical oncology fellow at Dana Farber Cancer Institute in Boston, Mass. “However, it is too early to determine if ASIs should be used for patients with metastatic renal cell carcinoma who do not also have hypertension or another medical condition to warrant ASI treatment.”
Researchers reviewed information from a clinical trials database of 4,736 patients with metastatic renal cell carcinoma treated on phase II and III clinical trials sponsored by Pfizer, Inc. ASI users were defined as patients taking an ASI when they started treatment or within the first 30 days of treatment. The cancer treatments reflected the current treatments being used and researched for RCC and varied to include VEGF targeted agents (such as sunitinib, sorafenib, axitinib, bevacizumab), mTOR-targeted agents (temsirolimus), and interferon.
The overall survival for patients receiving ASIs was 27 months, compared with 17 months for non-ASI users. In addition, the cancer was more likely to shrink in patients taking ASIs. Researchers also analyzed data from patients taking any type of antihypertensive (2,000 patients) and found that the overall survival for patients using ASIs was 27 months compared to 18 months for those on other types of anti-hypertensive agents. When evaluating patients based on therapy type, the benefit of ASIs was most significant in patients treated with VEGF-targeted therapy when compared with mTOR-targeted therapy or interferon.
Angiotensin system inhibitors fall into two classes - angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs). An ACE inhibitor lowers blood pressure by reducing the production of angiotensin II, which increases blood pressure, whereas ARBs block the effect of angiotensin II at the receptor. Increasingly, research has indicated that the peptide hormone angiotensin II is involved in certain steps in the process of carcinogenesis, including angiogenesis. Overall, ASIs are commonly used medications in the United States. They are generally well-tolerated; however, side effects include fatigue, low blood pressure, dizziness, increased potassium levels, cough, and angioedema (an allergic reaction).
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