From the Guidelines
Carboplatin-paclitaxel chemotherapy may be indicated despite the elevated liver enzymes (ALT 58 U/L and AST 86 U/L, both above the normal range for women of <35 U/L), but careful monitoring and consideration of liver function are necessary, as most clinical trials use a threshold of ALT <3× ULN for eligibility in the absence of primary liver tumour or liver metastatic disease, or <5× ULN in the presence of primary liver tumour or liver metastatic disease 1. Given the patient's ALT value is 58 U/L, which is approximately 1.65 times the upper limit of normal (assuming a ULN of 35 U/L), a dose adjustment for paclitaxel may be considered to minimize the risk of liver toxicity.
- The patient's liver function should be thoroughly assessed, including bilirubin, alkaline phosphatase, and albumin levels, to determine the extent of liver dysfunction.
- The cause of the liver enzyme elevation should be investigated, as it could be due to the underlying malignancy, medications, or other conditions.
- During treatment, liver function tests should be monitored regularly, typically before each chemotherapy cycle, to promptly identify any changes in liver function that may require further dose adjustments or treatment modifications.
- It is essential to weigh the benefits of chemotherapy against the potential risks of liver toxicity, and a multidisciplinary approach involving oncology, hepatology, and pharmacy specialists may be necessary to optimize the patient's treatment plan, as suggested by the review article on recommendations for detection, assessment, and management of suspected drug-induced liver injury during clinical trials in oncology patients 1.
From the Research
Liver Enzyme Levels and Paclitaxel Treatment
- The patient's liver enzyme levels are elevated, with ALT at 58 U/l and AST at 86 U/l, exceeding the normal range of <35 U/l.
- According to the study 2, paclitaxel is associated with mild elevations in serum aminotransferase levels, but significant hepatotoxicity is uncommon, particularly in patients without prior liver disease.
- The study 3 found that impaired liver function is associated with an increased risk of developing grade 3/4 hematological toxicity and dose modification in patients treated with paclitaxel for breast and ovarian cancer.
Diagnostic Considerations
- Elevated liver enzymes can be caused by various factors, including hepatocellular integrity disturbance, cholestatic liver diseases, and extrahepatic diseases, as discussed in the study 4.
- The study 5 highlights that muscle damage-induced transaminitis can also cause elevated transaminase levels, which may not necessarily imply an underlying liver pathology.
- The patient's elevated liver enzyme levels may require further evaluation to clarify the underlying cause, as suggested in the study 4.
Paclitaxel Treatment and Liver Function
- The study 3 suggests that patients with impaired liver function treated with paclitaxel are at greater risk of developing hematological toxicity and may require dose modifications.
- The study 2 reports a case of a patient with ovarian cancer who developed significant elevation of serum aminotransferases after paclitaxel plus carboplatin chemotherapy, highlighting the importance of monitoring liver function during treatment.
- The development of low-cost point-of-care monitoring of ALT and AST, as discussed in the study 6, may aid in faster decision making and diagnosis of acute liver injury in patients undergoing paclitaxel treatment.