Observational studyBMC cancer2024
Impaired liver function: effect on paclitaxel toxicity, dose modifications and overall survival.
Observational study in BMC cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- Paclitaxel in oncology: balancing anticancer efficacy with potential carcinogenic risks and resistance mechanisms.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Methotrexate-triggered ferroptosis suppresses oral cancer progression by phosphorylated KEAP1-mediated NRF2 degradation to inhibit SLC7A11/GPX4 signaling pathway.Cancer cell international · 2026Article
- Use of non-prescription analgesic medications and survival among Black women with ovarian cancer.British journal of cancer · 2026Article
- Successful reversal of hepatic visceral crisis in HER2-positive metastatic breast cancer: a case report.Frontiers in oncology · 2026Article
- QSAR Modeling for Predicting ICInternational journal of molecular sciences · 2025Article
- Article
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Authors and funding
12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe 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).
methodsFor 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.
resultsA 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.
conclusionsThis 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.
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