Patients who were on medications called angiotensin system inhibitors (ASIs), including angiotensin-converting-enzyme (ACE) inhibitor and angiotensin system blockers, commonly used to treat high blood pressure and other medical conditions survived an average of 26.68 months, compared with 17.05 months in those who did not receive the drugs, said Rana McKay, MD, a clinical oncology fellow at Dana-Farber. She will present a poster with the results on Saturday, February 1, at the 2014 Genitourinary Cancers Symposium sponsored by the American Society of Clinical Oncology in San Francisco.
High blood pressure, or hypertension, affects many people in the United States and can be a side effect of some drugs used in treating kidney cancer. Nearly half the patients in the clinical trials database used in the study had baseline hypertension prior to starting their cancer therapy, said the researchers.
“Though larger prospective studies are needed to further investigate this hypothesis, 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 McKay. But she cautioned it is too early to recommend ASIs for kidney cancer patients who don’t need an antihypertension drug. Such drugs can have adverse effects in people with normal blood pressure.
The greatest survival benefits were seen in patients who were taking ASIs while being treated with drugs that targeted the VEGF [Vascular Endothelial Growth Factor] pathway, according to the study. VEGF is a signaling protein that, when overexpressed, stimulates angiogenesis – the growth of new blood vessels that allow tumors to grow. VEGF inhibitors such as sunitinib, sorafenib, and axitinib are used in cancer treatment to block angiogenesis and starve the tumor.
In their retrospective study, McKay and her colleagues used a database of results of phase 2 and 3 clinical trials sponsored by Pfizer, Inc. The pooled data included 4,736 patients treated between 2003 and 2013 for metastatic kidney cancer. The patients were generally males, younger than 65, whose disease was considered intermediate-risk.
The majority were treated with the targeted anti-VEGF agents sunitinib, sorafenib, and axitinib. Others received temsirolimus, a drug that inhibits a different target, the mTOR protein, and interferon, which stimulates the immune system to fight tumors. Survival gains were greatest in patients who took ASIs while in treatment with anti-VEGF drugs, compared with mTOR inhibitors or interferon, the analysis revealed.
Angiotensin system inhibitors, which include lisinopril, captopril, and losartan, act on a hormone system that regulates blood pressure in the body. They are used to treat high blood pressure, congestive heart failure and other conditions.
The ASIs’ survival benefit in the kidney cancer patients was seen even after adjusting for baseline and treatment-related hypertension, said the investigators, and appeared to be synergistic with the action of the VEGF inhibitors. These observations fit with laboratory and animal findings showing that ASIs can slow tumor growth, inhibit angiogenesis, and curb metastasis – the spread of cancer beyond its original site.
“We were really impressed with the results obtained with ASI treatment in these patients,” said McKay. “I think this really is grounds for further exploration in a prospective trial.”
Toni Choueiri, MD, clinical director of the Lank Center for Genitourinary Oncology at Dana-Farber and director of the kidney cancer center at Dana-Farber is senior author of the report. Other authors are from Rutgers University and Pfizer Oncology.
The research was supported by Pfizer.