Toxicity spectrum of taxanes: A safety analysis from pre-marketing to post-marketing.

Abstract

Background: As fundamental chemotherapy drugs, paclitaxel and its derivatives are essential for cancer treatment. This analysis comprehensively evalutaed the toxicity spectrum of taxanes from the perspective of clinical trials and the real-world.

Research design and methods: Pooled-analyses were performed to estimate incidences of adverse events (AEs) with random-effect models after searching databases. Reports of AEs were retrospectively obtained from the US Food and Drug Administration's (FDA's) Adverse Event Reporting System (FAERS) database and positive signals were quantified by employing three algorithms.

Results: A total of 36 studies involving 10,828 patients were analyzed in pooled-analysis and 58,835 case reports were retrieved. Leukopenia (59.69, 95% confidence interval 41.34-75.69) and neutropenia (29.69, 23.31-36.99) ranked first among all grades and severe AEs, respectively. Alopecia, regardless of grades, had the highest estimated incidence of non-hematological AEs. The estimated incidences of AEs of Nab-paclitaxel tended to be higher than other formulations, especially neutropenia (46.53, 35.01-58.42). Docetaxel had the least signals but alopecia and depression have quantified several signals.

Conclusions: The safety of nab-paclitaxel was beyond expectation and unusual signals of alopecia and depression of docetaxel need to be paid attention to. Results of clinical trials and FAERS indicated consistency between premarket and postmarket studies.