Cancer clinical trials commonly use ‘two most inaccurate’ tests to measure kidney function
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Key takeaways:
- Common tests used in cancer clinical trials to evaluate kidney function may unnecessarily exclude some participants.
- No uniform oncology guidelines exist for estimating kidney function.
Most cancer clinical trials use inaccurate tests to evaluate kidney function when determining participant eligibility, according to results of a cross-sectional study.
Patients may be wrongly excluded from clinical trials or receive “inappropriate” drug dosing during the study due to results of these tests, researcher Alexander B. Karol, MD, resident physician in the department of medicine at Icahn School of Medicine at Mount Sinai, told Healio.
“It blew us away,” Karol said. “[The most common tests] are clearly the two most inaccurate approaches that you can use that are part of standard of care to estimate kidney function of patients with cancer.”
Background and methods
Glomerular filtration rate is the measurement used to determine kidney function. However, directly analyzing it is not practical due to cost, time and resources needed, Karol said.
“We have to do these studies that often involve injecting radioactive contrast and following [patients] for 24 hours,” he added. “Patients have to follow up the next day, and they can be lost to follow-up.”
A multitude of formulas exist to estimate renal function, but some have shortcomings, and a lack of oncologic guidelines causes heterogeneity in clinical trial design.
Karol and colleagues investigated which approaches cancer clinical trials use most often.
They used ClinicalTrials.gov to evaluate phase 3 trials of anticancer drugs for adults that had been completed between Oct. 28, 2013, and Oct. 28, 2023.
Their analysis included 231 trials that enrolled a combined 111,424 patients. Trials encompassed multiple cancer types, with the most common being lung cancer, hematologic malignancies, gastrointestinal cancers and breast cancer.
Surprising findings
The majority (86.5%) of trials used the Cockcroft-Gault formula or serum creatinine levels to define kidney function eligibility.
“We were very surprised because those methods were not recommended by nephrology societies,” Karol said.
The Cockcroft-Gault formula dates to 1973 and estimates glomerular filtration rate.
“[However], it’s been shown to underestimate kidney function [among] patients with cancer and leads to inappropriate trial exclusion,” Karol said.
Additionally, the development of the Cockcroft-Gault formula involved a study of 249 white men.
“There was no female population. Patients who are African American weren't represented,” Karol said. “It’s very unlikely to be as accurate in those populations because those populations weren’t studied in the equation that we still predominantly use.”
Serum creatinine levels do not accurately calculate kidney function for individuals with cancer, either, Karol said. That’s because this test relies on muscle mass, which people with cancer may lack due to the disease.
Researchers determined 34.4% of clinical trials since 2018 used serum creatinine alone to determine renal function, though they noted the trend has improved recently.
“Nephrology and oncology organization guidelines recommend against using serum creatinine level alone,” researchers wrote.
Guidelines needed
Nephrology guidelines recommend using modern formulas to estimate kidney function, but not any specific one, Karol said.
“Latest FDA guidelines from 2020 recommend estimating kidney function using a formula that does not include serum creatinine, but they didn’t recommend which formula to use,” he added.
Modern approaches include Chronic Kidney Disease–Epidemiology Collaboration and Modification of Diet in Renal Disease equations.
Potential biomarkers of kidney function — including cystatin C — also have been investigated. However, some cancers may release cystatin C, causing inaccurate readings, Karol said.
“We’re unable to really compare kidney associated toxicities between trials because we’re using very different methods,” he added. “We’re comparing apples to oranges.”
Karol highlighted the need for more research into safety biomarkers, and for stakeholders to develop uniform guidelines with modern approaches to evaluate kidney function.
“We believe that this will change soon because it would lead to significantly better patient outcomes by allowing us to appropriately dose, titrate and ensure patients are eligible for clinical trials,” Karol said. “We are very hopeful that guidelines will come out soon.”
For more information:
Alexander B. Karol, MD, can be reached at alexander.karol@mountsinai.org.
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