September 24, 2015

Cancer therapies’ impact on heart, kidneys explored

Vanderbilt is embarking on a multi-disciplinary approach to understand how promising cancer treatments, specifically certain kinase inhibitors, affect the heart and kidneys.

From left, David Slosky, M.D., Igor Puzanov, M.D., MSCI, Javid Moslehi, M.D., Khaled Abdel-Kader, M.D., M.S., and colleagues are studying how some promising cancer treatments, specifically kinase inhibitors, affect the heart and kidneys. (photo by Susan Urmy)

Vanderbilt is embarking on a multi-disciplinary approach to understand how promising cancer treatments, specifically certain kinase inhibitors, affect the heart and kidneys.

In recent years, kinase inhibitors have emerged as important options for treating many cancers. In particular, specific kinase inhibitors, called angiogenesis (or VEGF) inhibitors, target the tumor vasculature and have become options for hard-to-treat kidney malignancies.
Unfortunately, these drugs also target vasculature of the heart and the kidney.

“We have realized that the VEGF inhibitors cause elevation in blood pressure in the majority of patients. These drugs also can cause patients to develop clots or thrombotic events, leading to heart attacks, strokes and blockages in the vessels,” said Javid Moslehi, M.D., assistant professor of Medicine and director of the Cardio-Oncology program. “In addition, the patients also have renal problems, including proteinuria or leakage of proteins in urine.”

In a paper published recently in the Journal of the American College of Cardiology (JACC), Moslehi and colleagues from other medical centers outline the vascular and metabolic implications of novel targeted cancer therapies and recommend how patients receiving various kinase inhibitors (including VEGF inhibitors) should be monitored and treated.

“These drugs have only come about over the last 10 years; many of them over the last two years. It’s a whole new area for us to understand and explore,” he said.

How to prevent and treat cardiac and vascular toxicities of these novel treatments are an important part of the cardio-oncology program, a clinic dedicated to cardiovascular health of cancer patients.

VEGF inhibitors are particularly important for metastatic kidney cancer, for which there were no viable treatments prior to 2004. If the cancer had metastasized, there were no effective drugs. Since that time five new drugs that work on this pathway have become available.

“They can prolong the average patient’s life from the previous 14 months, to now 32-36 months. However, they all can damage the heart as well as the remaining kidney function,” said Igor Puzanov, M.D., MSCI, associate professor of Medicine and clinical director of renal cancer in the Division of Hematology-Oncology.

Because many patients who receive kinase therapy experience some sort of cardiac, vascular or renal issues, Vanderbilt now integrates these patients’ care with those of an onco-nephrology clinic and cardio-oncology clinic, as well as care by the treating oncologist.

“In a true, collaborative manner, cardiology, oncology and nephrology will be offering these joint services for these patients,” said Ray Harris, M.D., Ann and Roscoe Robinson Professor of Medicine and chief of the Division of Nephrology and Hypertension.

The JACC paper outlines an algorithm for the different groups of kinase inhibitors with respect to patient care.

In the case of kinase inhibitors used for kidney cancer, the patients should be monitored for cardiac issues caused by underlying risk factors including diabetes, smoking, hypertension, hyperlipidemia and kidney disease and treated effectively.

“Pre-treatment risk assessment, consistent monitoring and effective treatment for these patients are critical, because if a patient does have a stroke, heart attack or kidney failure as a result of new cancer therapies, they will not be able to continue with their cancer treatment,” Moslehi said.

At Vanderbilt, a pre-appointment coordinator arranges for the patients to be seen in multiple clinics on the same day. In addition, the incorporation of a messaging system via electronic medical records allows easy referral of the patients from the oncology center to the cardio-oncology and onco-nephrology clinics.

“The flow of patients who are seen by an oncologist, nephrologist and cardiologist and the collaborative spirit within the group allows us to ask the next questions: what are the most effective means of kidney or cardiac protection?” Moslehi said.

“How can we integrate the various expertise of the physicians at Vanderbilt to do additional research, to understand the underlying biology, to develop more innovative clinical algorithms and really become world leaders in this area?”