Assessing Taxane-Associated Adverse Events Using the FDA Adverse Event Reporting System Database
Taxanes are crucial antineoplastic agents used in treating various cancers. However, they can cause adverse events. This study aimed to evaluate their real-world safety.
Introduction
Taxanes like paclitaxel, docetaxel, and nab-paclitaxel interfere with microtube function. Paclitaxel was extracted from the Pacific yew tree, and docetaxel from the European yew tree. Paclitaxel is solvent-based, while nab-paclitaxel is a solvent-free albumin-bound nanoparticle. Taxanes are widely used in cancer treatment but adverse events can disrupt chemotherapy. Hypersensitivity reactions are known, and bone marrow toxicity and peripheral neuropathy can also occur.
The US FDA’s Adverse Event Reporting System (FAERS) is a large pharmacovigilance system. We used it to assess taxane-associated adverse events due to limited real-world knowledge.
Methods
Data Source: A retrospective study used FAERS data from January 2004 to December 2019. After deduplication, we had reports of hypersensitivity reactions (966), bone marrow toxicity (1109), and peripheral neuropathy (1374).
Drug and Adverse Event Identification: We used www.drugbank.ca for taxane names. MedDRA terms identified adverse events.
Data Mining: Statistical procedures like reporting odds ratio (ROR), proportional reporting ratio (PRR), multi-item gamma Poisson shrinker (MGPS), and Bayesian confidence propagation neural network (BCPNN) were used.
Statistical Analysis: Descriptive analyses were done. Non-parametric tests compared times to onset. Pearson’s x2 test compared adverse and death outcomes.
Results
Clinical Characteristics: Most hypersensitivity and peripheral neuropathy reports were with paclitaxel. Most bone marrow toxicity reports were with docetaxel. Healthcare professionals reported most events. Female patients had more adverse events.
Signal Detection: Paclitaxel had a positive ROR for hypersensitivity. Nab-paclitaxel had the highest signal for bone marrow toxicity and peripheral neuropathy.
Time to Onset: Nab-paclitaxel had a later onset for hypersensitivity, bone marrow toxicity, and peripheral neuropathy compared to others.
Outcome: Paclitaxel had a lower death rate from hypersensitivity. Nab-paclitaxel had a higher death rate from peripheral neuropathy.
Discussion
This is a novel study on taxane-associated adverse events in the real world. Nab-paclitaxel showed the highest signal. Paclitaxel had a positive ROR for hypersensitivity, but docetaxel and nab-paclitaxel had negative signals. Nab-paclitaxel had an increased death rate, which is surprising as it’s considered safer. Clinicians focus on paclitaxel’s infusion reactions, but premedication helps. However, there’s insufficient preparation for bone marrow toxicity and peripheral neuropathy. Data mining has limitations, like regional data missing.
Conclusions
Our study identified positive signals for taxane-associated adverse events. Nab-paclitaxel had the highest signal. More research is needed for better taxane application.
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doi:10.1097/CM9.0000000000001562
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