Drug repositioning studies to prevent oxaliplatin-induced peripheral neuropathy

<p>Oxaliplatin, a platinum-based anticancer drug, is an important agent in the standard chemotherapy for colorectal, gastric, and pancreatic cancers, but it also often induces peripheral neuropathy. Oxaliplatin-induced peripheral neuropathy is classified into acute (cold hypersensitivity) and chronic (numbness, pain, and dysesthesia) neuropathie. The neuropathy affects quality of life and leads to dose reduction or discontinuation of chemotherapy. However, there are no prophylactic or therapeutic agents strongly recommended for the peripheral neuropathy in guidelines from ASCO, ESMO, and JASCC.</p><p>In our basic research, mechanisms underlying the acute and chronic neuropathies have been clarified. Furthermore, we have identified several potential prophylactic and therapeutic agents from approved drugs by targeting the mechanisms in basic research, adverse drug reaction database analysis research, and clinical research. In particular, we have recently identified a proton pump inhibitor as a potential prophylactic agent for oxaliplatin-induced neuropathy. In rats, omeprazole, a proton pump inhibitor, prevented neuropathic pain and peripheral nerve degeneration caused by oxaliplatin. In addition, in an analysis of FAERS, a database of adverse drug reactions, the rate of peripheral neuropathy was lower in patient reports of concomitant use of proton pump inhibitors. Furthermore, in a retrospective cohort study of 1,038 patients starting oxaliplatin treatment at Kyushu University Hospital, the concomitant proton pump inhibitor group had significantly lower incidence of peripheral neuropathy (any grade) and treatment discontinuation due to peripheral neuropathy than the non-concomitant group.</p><p>This symposium will present the findings of our drug repositioning studies and future perspectives.</p>