Establishment of the menthol test as a clinical evaluation method for oxaliplatin-induced neuropathy

Objectives: To determine whether the tongue menthol test, which measures the cold sensation detection threshold (CDT) of the tongue, used before and after oxaliplatin administration is an objective evaluation method for oxaliplatin-induced peripheral neuropathy (OPN). Methods: The tongue menthol test was administered to patients both before and after undergoing chemotherapy containing oxaliplatin for colorectal cancer. The tongue menthol test was conducted by applying a menthol solution (a selective agonist of transient receptor potential cation channel subfamily M member 8 [TRPM8]) to the tongue and measuring the CDT. Results: The mean CDT before the first dose of oxaliplatin was 0.34% (0.005%–1%; n=38), and the mean CDT after the first dose was 0.32% (0.005%–1%; n=38). The CDT appeared to decrease after the first dose, but this difference was not significant. In patients who received five courses of oxaliplatin, changes in CDT values were compared before and after the five courses. In patients with Neurotoxicity Criteria of Debiopharm (DEB-NTC) grade 2 neuropathy, the pre-oxaliplatin administration CDT was compared between before grade exacerbation and when exacerbation occurred, and was found to decline when grade exacerbation occurred. Moreover, when the CDTs before and after administration were compared before grade exacerbation, there was a significant decrease in CDT after administration (P=0.04). Conclusions: By performing a menthol test in oxaliplatin-treated patients, it may be possible to objectively predict the exacerbation of peripheral neuropathy at an early stage.