FIP Brisbane 2023 81st FIP World Congress of Pharmacy and Pharmaceutical Sciences in Brisbane, Australia, 24 to 28 September 2023

Background: Patients with cancer experience chemotherapy-induced peripheral neuropathy (CIPN), an intractable adverse event of anticancer drugs. However, no effective therapeutic drug exists. We have previously reported that simvastatin, an HMG-CoA reductase inhibitor (HRI), can ameliorate oxaliplatin-induced CIPN. Purpose: Here, we demonstrate the efficacy of HRIs in oxaliplatin-and paclitaxel-induced peripheral neuropathy in mice. Additionally, patient safety was predicted using medical claims data. Method: Oxaliplatin or paclitaxel were administered to male C57BL/6J mice. The HRIs (simvastatin, atorvastatin, and rosuvastatin) were administered orally. Changes in cold and mechanical sensitivity were assessed using the acetone test or von Frey tests. The influence of HRIs on the antitumor effect was measured using the survival rate of cancer cells (colon, gastric, ovarian, and lung) treated with anticancer drugs. The incidence of peripheral neuropathy and overall survival were examined in anticancer drug user reports in the JMDC claims database. Results: HRIs did not affect the anticancer drug-induced cold sensitivity. In contrast, HRIs ameliorated the decreased threshold to mechanical stimuli in mice treated with oxaliplatin or paclitaxel. The survival ratio of each cancer cell type was unchanged after cotreatment with the HRIs, oxaliplatin, or paclitaxel. Patients given HRIs had no exacerbation of neuropathy, despite having some neuropathy risk factors . Moreover, overall survival was not decreased by the HRIs. Conclusion: Our results indicated that HRIs are effective and safe for treating CIPN. However, the benefits of HRIs in non- lipidemic patients need further consideration.