Analysis of chemotherapy-induced peripheral neuropathy using the Japanese Adverse Drug Event Report database

Abstract

Abstract Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse event associated with several antineoplastic drugs; however, the precise risks and time course of reactions of particular drugs are not clearly understood. The aim of this study was to evaluate the relationship between anticancer agents and CIPN development using data from the Japanese Adverse Drug Event Report (JADER) database and to characterize the time-to-onset and outcomes of CIPN. Chemotherapy-induced peripheral neuropathy was defined using the Medical Dictionary for Regulatory Activities preferred terms. Disproportionality analysis was performed by calculating the reporting odds ratio (ROR) with 95% confidence interval for signal detection. Data of nine Anatomical Therapeutic Chemical (ATC) drug categories correlated with CIPN development, in addition to the data of the time-to-onset and outcomes. Among 622,289 reports in the JADER database from April 2004 to March 2020, there were 1883 reports of adverse events corresponding to peripheral neuropathy. The ROR (95% confidence interval) for vinblastine, sorbent-based paclitaxel (sb-PTX), oxaliplatin, and bortezomib was 20.4 (12.5–33.4), 13.6 (11.9–15.7), 26.2 (23.6–29.1), and 30.8 (26.6–35.8), respectively. The median duration (interquartile range) to CIPN development after the administration of vinca alkaloids and analogues, taxanes, platinum compounds, and monoclonal antibodies was 11.0 (5.0–46.5), 22.5 (6.0–82.5), 22.0 (6.0–68.5), and 32.5 (11.3–73.8) days, respectively. The median duration (interquartile range) of sb-PTX and nanoparticle albumin-bound (nab)-PTX was 35.0 (7.0–94.0) and 5.5 (3.0–29.3) days, respectively. Our analysis of records in the JADER database revealed several drugs associated with a high risk for CIPN development. In particular, the development of CIPN after vinca alkaloid administration should be closely monitored for 2 weeks after administration. CIPN caused by nab-PTX showed significantly faster onset than that by sb-PTX. Patients who receive taxanes or monoclonal antibodies often do not show an improvement; accordingly, early treatment is required.