From the Guidelines
Yes, docetaxel and Phesgo should be delayed when ALT is 134 U/L, which is approximately 3.8 times the upper limit of normal (ULN) of 35 U/L, as this elevation indicates moderate hepatotoxicity and continued treatment could worsen liver function. According to the latest guidelines, rechallenge with the same or a lower dose may be considered when liver test elevations have resolved to predefined levels, such as delaying rechallenge until ALT returns to <2–3× ULN for those with near normal baseline ALT (<1.5× ULN) 1.
In this case, since the patient's ALT is 3.8 times the ULN, it is reasonable to delay treatment until liver function tests improve to grade 1 or baseline (less than 3 times ULN). The patient should have repeat liver function tests in 1-2 weeks, and treatment can resume once ALT decreases to less than 3 times ULN.
Some key considerations for rechallenge include:
- The presence of advanced liver disease, which generally precludes rechallenge 1
- Clinical and biochemical features of the initial presentation of DILI, such as signs of hepatic decompensation or suspected allergic or hypersensitivity features, which may guide a decision regarding rechallenge 1
- The potential benefit associated with the drug in malignant diseases, and the availability of alternative treatment options 1
During this delay, it's essential to investigate potential causes of the elevated ALT, which could include medication effects, viral hepatitis, alcohol use, or disease progression. Hydration and avoiding hepatotoxic medications or substances may help improve liver function more quickly.
From the FDA Drug Label
In case of AST/ALT >2.5 to ≤5 × ULN and AP ≤2.5 × ULN, or AST/ALT >1.5 to ≤5 × ULN and AP >2.5 to ≤5 × ULN, docetaxel injection should be reduced by 20%. Avoid use of docetaxel if bilirubin > ULN, or if AST and/or ALT >1.5 × ULN concomitant with alkaline phosphatase >2.5 × ULN.
- ALT is 134 which is approximately 3.8 times the upper limit of normal (ULN), assuming a normal range of 0-35.
- According to the label, if AST/ALT >1.5 to ≤5 × ULN, docetaxel should be reduced, but the label does not explicitly state to delay.
- However, it is recommended to obtain LFTs before each treatment cycle, and the label advises against administering docetaxel with abnormal liver function.
- Given the elevated ALT, it would be prudent to delay treatment until liver function tests are within normal limits or improved to minimize the risk of hepatotoxicity.
- The decision to delay should be based on a conservative clinical assessment, taking into account the patient's overall condition and the potential risks and benefits of delaying treatment 2 2.
From the Research
Docetaxel and Liver Function
- The decision to delay Docetaxel Phesgo due to elevated ALT (134) should be based on the degree of liver dysfunction and the patient's overall clinical condition.
- According to the study by 3, patients with grade 2 and 3 elevations of transaminases at baseline in conjunction with elevation of alkaline phosphatase had 22 and 38% lower clearances of docetaxel, respectively.
- The study by 4 notes that ALT is a useful biomarker for detecting liver injury, but its elevation does not necessarily predict worse effects to come or indicate liver function.
Clinical Considerations
- The study by 5 suggests that docetaxel can be administered to patients with metastatic breast cancer and liver dysfunction after dose attenuation, and that therapy should be closely monitored with subsequent dose escalation when possible.
- The study by 6 highlights the importance of considering the differential diagnostic work-up of elevated serum transaminase levels and monitoring test performance, reference values, and analytical pitfalls of these biomarkers.
- The study by 7 reports that responses to GTX chemotherapy (including docetaxel) in patients with advanced pancreatic adenocarcinoma significantly correlated with toxicity, including ALT elevation.