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Observational Study
. 2024 Dec 18;24(1):1553.
doi: 10.1186/s12885-024-13330-2.

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

Marieke Schmidt  1 , Robin Vernooij  2   3   4 , Merel van Nuland  1 , Erin Smeijsters  1 , Lot Devriese  5 , Nadia Haj Mohammad  5 , Thom Hermens  1 , Julian Stammers  1 , Christina Swart  1 , Toine Egberts  1   6 , Saskia Haitjema  2 , Laureen Lammers  7
Affiliations
Observational Study

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

Marieke Schmidt et al. BMC Cancer. .

Abstract

Background: The anticancer drug paclitaxel is primarily metabolized in the liver. Previous studies have indicated a correlation between impaired liver function and paclitaxel toxicity, which may indicate dose reduction. Since the evidence is limited, the aim of this study was to investigate the effect of impaired liver function on the hematological toxicity of paclitaxel, dose modifications and overall survival (OS).

Methods: For this single-center retrospective observational study, patients treated with paclitaxel for breast, esophageal and ovarian cancer at the University Medical Centre Utrecht between 2011 and 2022 were identified from the Utrecht Patient Oriented Database (UPOD). Based on regression analysis, the risk of developing Grade 3/4 hematological toxicity was compared between patients with normal and impaired (based on the NCI criteria for bilirubin and ASAT (aspartate aminotransferase) concentrations) liver function. Additionally, differences in the occurrence of toxicity-related dose modifications and OS were evaluated between the two groups.

Results: A total of 569 patients were included. Breast cancer patients who were receiving advanced treatment and had mildly impaired liver function (ASAT ≤ 2x ULN, bilirubin ≤ ULN) had an increased risk of developing grade 3/4 neutropenia (HR = 4.39, 95% CI 1.20-16.02; p = 0.03). In addition, patients with impaired liver function treated according to the advanced ovarian cancer regimen had an increased risk of developing grade 3/4 leukopenia (HR = 12.64, 95% CI 2.12-75.22, p = 0.01) and dose modification (treatment discontinuation) (HR = 3.91, 95% CI 1.74-8.79, p < 0.01). Impaired liver function was also associated with decreased OS in inoperable esophageal and advanced ovarian cancer patients (HR = 7.65, 95% CI 2.54-23.1, p < 0.01 and HR = 2.98, 95% CI 1.36-6.54, p < 0.01, respectively). The risk of developing grade 3/4 hematological toxicity during lower-dose paclitaxel treatment protocols was not significantly different in patients with impaired liver function.

Conclusions: This study revealed that patients with impaired liver function treated with paclitaxel for breast and ovarian cancer in an advanced setting are at greater risk of developing hematological toxicity than patients with normal liver function at the start of therapy. Furthermore, in patients with ovarian (advanced) or inoperable esophageal cancer, impaired liver function is associated with decreased OS. Within these groups of patients, it is important to weigh the risk of upfront paclitaxel dose modifications versus an adaptive strategy.

Keywords: Impaired liver function; Paclitaxel toxicity; paclitaxel dose modifications.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: The medical research ethics committee of UMC Utrecht (MREC Utrecht) confirmed that the Medical Research Involving Human Subjects Act (WMO) does not apply to this study. Therefore, official approval for this study under the WMO is not needed (see the attached file for the declaration by MREC Utrecht - protocol number 21–555/C). Consent for publication: N.A. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Flowchart of patient inclusion
Fig. 2
Fig. 2
One-minus survival curves of grade 3/4 neutropenia in the advanced breast cancer protocol (A) and grade 3/4 leukopenia in the advanced ovarian cancer protocol (B)
Fig. 3
Fig. 3
Overall survival in patients with impaired and normal liver function and ovarian cancer (advanced treatment) (A) and inoperable esophageal cancer (B)
See this image and copyright information in PMC

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