From the Guidelines
ULN stands for Upper Limit of Normal, which refers to the highest value of a particular test that is considered within the normal range. In the context of laboratory values, ULN is used to standardize results across different laboratories that might have slightly different reference ranges. For example, if a lab's normal range for ALT is 0-40 U/L, then 1.5 times ULN would be 60 U/L, as indicated in the provided evidence 1. The information provided indicates that patients with elevated liver function tests (transaminases >1.5× ULN along with alkaline phosphatase >2.5× ULN) are at higher risk for severe adverse reactions to docetaxel at the 100 mg/m² dose. This is because docetaxel is primarily metabolized by the liver, and impaired liver function can lead to higher drug concentrations in the blood, increasing toxicity risk, as discussed in the context of hepatotoxicity management in oncology trials 1. Clinicians use these ULN-based thresholds to guide dosing decisions and determine when dose reductions or alternative treatments might be necessary, taking into account the degree of variation that exists for ALT reference ranges between laboratories, where ULN values may vary between less than 30 U/L for some laboratories to more than 70 U/L for others 1. Some key points to consider when interpreting ULN include:
- The use of serum ALT is preferred over AST due to its higher hepatic specificity 1
- Isolated ALP elevation is often related to the underlying malignancy and uncommonly related to liver injury 1
- Measurement of total and conjugated (or direct) bilirubin is recommended to help identify patients with indirect hyperbilirubinemia due to Gilbert's syndrome or hemolysis versus liver injury 1
- The CTCAE grading of liver test elevations has limitations, particularly in patients with abnormal baseline liver biochemical tests, and should be used with caution in the context of DILI assessment and management 1. Therefore, it is essential to consider the ULN values in the context of individual patient factors, laboratory reference ranges, and the specific clinical scenario to ensure accurate interpretation and appropriate management of liver function tests in patients treated with docetaxel.
From the FDA Drug Label
5.1 Toxic Deaths ... patients who had abnormal baseline liver function (AST and/or ALT >1.5 times ULN together with AP >2.5 times ULN) 5.2 Hepatic Impairment ... Avoid Docetaxel Injection in patients with bilirubin > upper limit of normal (ULN), or to patients with AST and/or ALT >1.5 × ULN concomitant with alkaline phosphatase >2.5 × ULN
ULN means Upper Limit of Normal.
From the Research
Definition of ULN
- ULN stands for Upper Limit of Normal, which is a reference value used to determine the normal range for various laboratory tests, including liver function tests such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST) 2, 3.
- The ULN is typically defined as the 95th percentile of the reference population, meaning that 95% of the population will have values below this level 2.
- The ULN can vary depending on the laboratory, the specific test, and the population being tested 3.
Factors Affecting ULN
- Factors such as age, gender, and body mass index (BMI) can affect the ULN for certain laboratory tests, including ALT 2, 3.
- The ULN can also be influenced by the presence of certain medical conditions, such as liver disease or metabolic disorders 4, 5.
Clinical Significance of ULN
- The ULN is used as a reference value to determine whether a patient's laboratory results are within the normal range or indicate a potential abnormality 4, 5.
- Abnormal laboratory results, including elevated liver enzymes, can be categorized based on the pattern and magnitude of elevation, with mild, moderate, and severe elevations having different clinical implications 5.