This study provides an updated, comprehensive analysis of the characteristics and differences in adverse events following treatment with nanoliposomal DOX compared to CDOX. Due to its enhanced permeability, retention, and lower cardiotoxicity, nanoliposomal DOX plays a significant role in the clinical setting. The majority of preferred terms (PTs) were chosen based on a previous report 13, thus complementing findings that were previously unattainable due to a lack of cases. Despite its benefits, nanoliposomal DOX can cause additional discomfort to patients, thereby reducing their quality of life. Consequently, a comprehensive disproportionality analysis for nanoliposomal DOX and CDOX is crucial for optimal clinical application and management.
Our results concerning the trends of adverse events in liposomal DOX and CDOX largely align with previous literature. Additionally, by comparing the outcomes of adverse events and analyzing their onset times, we identified several significant differences. Overall, the response to adverse events was better with liposomal DOX and CDOX, and several key findings emerged that warrant further discussion.
In our study, the onset time for mucosal inflammation after treatment with liposomal DOX and CDOX was the shortest, while that for malignant neoplasm progression was the longest. The onset times for cardiomyopathy, sepsis, and thrombocytopenia were longer for Doxil® compared to CDOX. Moreover, the onset times for palmar-plantar erythrodysesthesia (PPE), pancytopenia, and sepsis were longer for Myocet® compared to CDOX.
Randomized controlled trials have demonstrated that nanoliposomal DOX exhibits comparable anti-tumor activity and significantly reduced cardiotoxicity compared to CDOX in multiple breast cancer patients 15,28. Palmar-plantar erythrodysesthesia (PPE), frequently observed in Doxil® usage, was not seen with Myocet® 22. A retrospective trial of Myocet® in lymphoma patients revealed that the most common grade 3/4 toxicity was hematological, including leukopenia, neutropenia, thrombocytopenia, and febrile neutropenia. In contrast, the main toxicity of Doxil® was mucocutaneous 28,29. Our study showed that the reporting odds ratios (RORs) for cardiotoxicity and febrile neutropenia were significantly lower for nanoliposomal DOX, particularly Doxil®, compared to CDOX. However, Myocet® did not appear to reduce the risk of cardiotoxicity and febrile neutropenia as effectively. The ROR for PPE was noticeably higher with Doxil® compared to CDOX. The ROR for PPE in patients receiving Myocet® was also high and could potentially be closely related to the dose or duration of Myocet® treatment 30,31.
In our analysis, the age of most patients was concentrated between 18 and 64, with a mean onset age just over 50 years and a mean weight of 59.6 kg. Over the past 19 years, the number of reported cases has steadily increased. In terms of cancer prevalence, patients with malignant lymphoma exhibited the highest reporting rate, especially those with diffuse large B-cell lymphoma. The combination of Doxil® and carboplatin resulted in a higher incidence but shorter duration of mucosal perfusion and PPE 29. Among the 13 adverse events analyzed, the shortest onset time for liposomal DOX and CDOX was observed in mucosal inflammation. The onset time of PPE for Myocet® was longer than that for CDOX, whereas the onset time for Doxil® was shorter. This suggests that Doxil® more readily and quickly induces mucosal inflammation and PPE. Additionally, the onset times of malignant neoplasm progression and lung disease for Doxil® were shorter than for CDOX, indicating these conditions are more easily triggered by Doxil®.
The Myocet® presents low cardiotoxicity while retaining its efficacy. Nonhematologic toxicities were less frequent, but more often led to fatal events. Compared to CDOX, liposomal DOX shows equivalent antitumor activity with fewer side effects, but further strategies are needed to mitigate these adverse reactions. Continuous monitoring, risk evaluations, and additional comparative studies of liposomal DOX and CDOX should be considered. This will provide a reference for the safe and effective clinical use of liposomal DOX and CDOX.
Due to inherent limitations of clinical trials, such as patients having multiple disease types, some patients experiencing several adverse events simultaneously, the relatively small sample size for certain adverse events, differences in the occupation and professional levels of the reporters, non-standardized time recording, and the possibility of false positive signals in the signal detection method, we may not be able to fully unravel the intricacies of this study. Thus, further clinical trials are required to inform drug selection in clinical practice.