Imprecise Kidney Function Thresholds in Cancer Clinical Trials and the Potential for Harm

Area of Science:

• Nephrology
• Oncology
• Clinical Pharmacology

Background:

• Current medical guidelines recommend using glomerular filtration rate (GFR) for assessing kidney function and guiding drug dosing.
• Serum creatinine (Scr) alone or creatinine clearance are often used but are less precise than GFR.

Purpose of the Study:

• To evaluate the definitions of kidney function thresholds used for eligibility in cancer clinical trials.
• To identify the prevalence of GFR versus Scr or creatinine clearance in defining these thresholds.

Main Methods:

• A random sample of 465 active Phase I-III trials involving cisplatin and 74 studies in cancer patients with decreased kidney function were analyzed.
• Data were sourced from clinicaltrials.gov to assess defined kidney function criteria.

Main Results:

• Kidney function thresholds were defined by Scr alone or a composite including Scr or creatinine clearance in 46% of cisplatin trials.
• Only 2% of cisplatin trials and 14% of trials for decreased kidney function utilized GFR.
• A significant discrepancy exists in the methods used to define kidney function eligibility across cancer trials.

Conclusions:

• Imprecise and inconsistent kidney function thresholds are commonly used in cancer clinical trials.
• These inconsistent criteria may lead to patient harm through drug toxicity or reduced treatment efficacy.
• Adoption and harmonization of recommended GFR standards are crucial for improving cancer trial design and patient safety.