A new study highlighting the link between kidney disease and cancer cites a growing need for clinical guidelines to better predict and prevent toxicity across a wide spectrum of cancer therapies.
The review article, published in The Lancet, looks at both acute kidney injuries and chronic long-term kidney disease caused by conventional cytotoxic chemotherapy, as well as newly developed anticancer agents, such as immune checkpoint inhibitors and chimeric antigen receptor (CAR) T-cell therapy (2020; doi: https://doi.org/10.1016/S0140-6736(20)30540-7). These newer, more precise cancer treatments have led to greater patient survival, but also to more cases of nephrotoxicity, according to the study's European scientists in Poland, Italy, and the Czech Republic.
Of "particular concern," the investigators wrote, is an increased incidence in renal problems tied to cancer treatments for individuals with breast, lung, colorectal, and gynecological cancers. "The combination of cancer with impaired renal function worsens patient outcomes and complicates their management and treatment," they noted.
Although experts have known for years that many cancer treatments exact a powerful toll on the body's major organ systems, the kidneys' susceptibility to injury can be exacerbated by a number of well-characterized risks: patients' older ages at the time of cancer diagnosis; pre-existing chronic kidney disease brought on by underlying health problems; or genetic mutations in cellular and renal transport genes, among others. Moreover, these fist-sized organs are often exposed to high and repeated concentrations of chemotherapeutic agents during treatment, while serving as the major route of excretion for metabolites, including those shed by dying cancer cells.
"It's not a one-size-fits-all approach," said Bradley McGregor, MD, Clinical Director at the Lank Center of Genitourinary Oncology at Dana-Farber Cancer Institute in Boston, referring to the challenging complexities that oncologists face. "When you have cancer, there are competing risks-the risk of cancer or the risk of these drugs. The risk of cancer is greater."
McGregor noted that the review article illustrates how cancer therapies inflict highly variable injuries to the kidneys, requiring careful monitoring of renal function - just one aspect of continuing care, he said, along with aggressive hydration, controlling blood pressure, and monitoring blood work.
But, as the study points out, even targeted drugs have off-target effects that impact the kidneys, despite their ability to home in on genetic errors that may drive cancer development.
"Personalized medicine does not mean without toxicity," McGregor stressed. "How we monitor immunotherapy differs from how we monitor methotrexate" to ensure the best chance for patient success.
Jan Beumer, PharmD, PhD, Director of UPMC Hillman Cancer Center's Pharmacokinetics and Pharmacodynamics Facility at the University of Pittsburgh, called the Lancet study timely, adding that the decision to devote so many pages to the topic, "is very telling."
"There's been a groundswell of interest both within the oncology community and the nephrology community" in the issue of kidney disease in cancer patients, he said. Reflecting that trend is the relatively new subspecialty of onconephrology, which combines the expertise of two fields already specialized into one.
An expert in kidney dysfunction, Beumer, Co-Chairman of the National Cancer Institute's pharmacology task force, said that, broadly speaking, physicians need to avoid certain cancer drugs if the kidneys are not working well-considered an increasing probability given the natural decline of kidney function with age and the older ages of so many cancer patients at diagnosis.
"Cisplatin jumps out as one," Beumer noted, despite its successful use as the solid backbone of many therapeutic cancer treatments, even in combination with newer drugs. In clinical practice, if testing shows a patient's creatinine clearance below 60 mL/min, he said most physicians would avoid using this drug, given its unacceptably high risk for kidney damage.
"There are many 'yes/no' decisions," he said. "[For instance,] are we going to give aggressive chemotherapy? If so, you better make sure you measure kidney function in the right way."
What exactly is the right way is still debated in the medical community. But, estimating kidney function lies at the heart of clinical decisions, Beumer said, with overestimating how well the kidneys work leading to improper drug selection and increasing toxicity, while underestimating their function can lead to therapeutic failure, as a treatable cancer advances.
Ultimately, the level of acceptable risk depends on patients' life expectancy and "where you start" in terms of age, type of cancer, the extent of kidney disease, and other factors, Beumer said. Oncologists, as a rule, are assertive by nature, he noted, as they seek to extend life in a meaningful way and "toxicity is part of that package."
Susan Jenks is a contributing writer.