Impaired liver function: effect on paclitaxel toxicity, dose modifications and overall survival

Area of Science:

• Oncology
• Pharmacology
• Hepatology

Background:

• Paclitaxel, a key anticancer drug, is mainly metabolized by the liver.
• Impaired liver function is linked to increased paclitaxel toxicity, suggesting potential dose adjustments.
• Limited evidence necessitates further investigation into liver function's impact on paclitaxel treatment outcomes.

Purpose of the Study:

• To investigate the effect of impaired liver function on paclitaxel-induced hematological toxicity.
• To evaluate the impact of impaired liver function on dose modifications and overall survival (OS) in cancer patients treated with paclitaxel.
• To compare toxicity risks between patients with normal and impaired liver function.

Main Methods:

• A single-center retrospective observational study involving 569 patients treated with paclitaxel for breast, esophageal, or ovarian cancer.
• Liver function assessed using NCI criteria for bilirubin and ASAT (aspartate aminotransferase) concentrations.
• Regression analysis used to compare the risk of Grade 3/4 hematological toxicity, dose modifications, and OS between patients with normal and impaired liver function.

Main Results:

• Patients with mildly impaired liver function (breast cancer, advanced treatment) showed a higher risk of Grade 3/4 neutropenia (HR=4.39).
• Impaired liver function was associated with increased Grade 3/4 leukopenia (HR=12.64) and dose modifications (HR=3.91) in advanced ovarian cancer.
• Decreased OS was observed in patients with impaired liver function undergoing treatment for inoperable esophageal cancer (HR=7.65) and advanced ovarian cancer (HR=2.98).

Conclusions:

• Impaired liver function elevates the risk of hematological toxicity in advanced breast and ovarian cancer patients treated with paclitaxel.
• Impaired liver function is linked to reduced OS in advanced ovarian and inoperable esophageal cancer patients.
• A careful balance between upfront dose modification and adaptive strategies is crucial for managing paclitaxel therapy in patients with impaired liver function.