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Possible prevention of paclitaxel-induced peripheral neuropathy by concomitant use of α1-receptor antagonist based on
Kohei Mori1,2, Takehiro Kawashiri3, Keisuke Mine1,2
1Department of Clinical Pharmacy and Pharmaceutical Care, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan.
Purpose:
Paclitaxel and albumin-bound paclitaxel are important anticancer drugs for the treatment of non-small cell lung, pancreatic, gastric, and gynecological cancers; however, they cause peripheral neuropathy as an adverse reaction. Therefore, prophylaxis and treatment for peripheral neuropathy are needed, since there are no sufficient evidence-based strategies to prevent it. Our previous animal research and adverse effect database analysis studies have identified the potential of α1 antagonists to attenuate paclitaxel-induced peripheral neuropathy (PIPN). The purpose of the present study was to investigate the prophylactic potential of α1 antagonists for PIPN in patients with cancer.
Methods:
Data were collected from the medical records of 673 male patients aged 18 years and older who started treatment with paclitaxel- or albumin-bound paclitaxel-containing regimens at Kyushu University Hospital between January 1, 2013, and December 31, 2019. The two primary outcome measures were PIPN occurrence and paclitaxel discontinuation due to PIPN. Kaplan-Meier curves were generated for cumulative doses and evaluated using the log-rank test.
Results:
The percentage of patients in whom PIPN occurred (any grade) during the entire study period was 37.4% and 20.0% in without and with α1-receptor antagonist groups, respectively (P = 0.0101, χ2 test). The incidence of PIPN (any grade) was significantly lower in the α1 antagonists combination group (N = 55) than in the no α1-receptor antagonists group (N = 618) (P = 0.0425, log-rank test). However, there were no significant differences between the two groups in the discontinuation of paclitaxel due to PIPN (P = 0.9654).
Conclusions:
The present retrospective cohort study may suggest that concomitant use of α1-receptor antagonists may moderate the development of PIPN.
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