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. 2021 May 31;11(1):11324.
doi: 10.1038/s41598-021-90848-6.

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

Misaki Inoue  1 , Kiyoka Matsumoto  1 , Mizuki Tanaka  1 , Yu Yoshida  1 , Riko Satake  1 , Fumiya Goto  1 , Kazuyo Shimada  1 , Ririka Mukai  1 , Shiori Hasegawa  1   2 , Takaaki Suzuki  1   3 , Hiroaki Ikesue  2 , Jun Liao  4 , Tohru Hashida  2 , Mitsuhiro Nakamura  5
Affiliations

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

Misaki Inoue et al. Sci Rep. .

Erratum in

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.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Flowchart outlining the construction of the dataset used for analysis.
Figure 2
Figure 2
Histogram and Weibull shape parameter of chemotherapy-induced peripheral neuropathy for each drug in the ATC classification. Right panel shows box plots, which represent the median (the horizontal line within the box). The ends of the box represent the 25th and 75th quantiles, also expressed as the 1st and 3rd quartile, respectively. The confidence diamond contains the mean and the upper and lower 95% CIs of the mean. The whiskers extend to the outermost data point that falls within the distances of 1.5 times the length of the inner quartiles. The bracket outside the box indicates the shortest half, which is the densest 50% of the observations.
Figure 3
Figure 3
Kaplan–Meier plot of chemotherapy-induced peripheral neuropathy for solvent-based (sb)-paclitaxel and nanoparticle albumin-bound (nab)-paclitaxel.
Figure 4
Figure 4
Mosaic plot of outcomes of chemotherapy-induced peripheral neuropathy. The plot is divided into rectangles where each vertical length represents the proportion of each level of the Y variable within each level of the X variable.
Figure 5
Figure 5
Two-by-two contingency table.
See this image and copyright information in PMC

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