1591P - Phase II study of topical menthol for chemotherapy-induced peripheral neurotoxicity (CIPN)

Date 01 October 2012
Event ESMO Congress 2012
Session Poster presentation III
Topics Complications/Toxicities of Treatment
Supportive Measures
Presenter Masato Nakamura
Authors M. Nakamura, K. Nakamura, T. Onikubo, H. Kamikawa, K. Tauchi
  • Aizawa Comprehensive Cancer Center, Aizawa Hospital, 390-8510 - Matsumoto/JP



Chemotherapy-induced Peripheral Neurotoxicity (CIPN) is a major dose-limiting toxicity of many commonly used chemotherapeutic agents that can limit successful disease control in cancer care. Although some systemic agents have been available, a significant proportion of patients are left with long-term pain and disability which is difficult to treat. Transient Receptor Potential Melastatin-8 (TRPM-8) is distributed in peripheral nerves and has been shown to associate with cold hypersensitivity, noxious cold, sensory disturbance, and impaired thermoregulation. Menthol is a compound derived from mint leaves that functions as an agonist of TRPM-8. Preclinical and clinical works have shown the effect of topical menthol on CIPN. We conducted a phase II study to investigate the effects of menthol on CIPN.


27 patients with CIPN caused by treatment with oxaliplatin (n = 22), paclitaxel (n = 3), capecitabine (n = 1), and irinotecan (n = 1) applied 1% topical menthol, twice daily to affected skin areas. CIPN symptoms were assessed separately for the hands and feet using the Numerical Rating Scale (NRS) and modified Peripheral Neuropathy Scale (PNS) based on patient questionnaires at baseline, 4 and 8 weeks after treatment. Responders and good responders were defined as 10% and 30% reduction in NRS respectively.


Three patients (11%) could not continue the study due to adverse events (skin swelling, desquamation and aggravation of Hand-Foot Syndrome). Efficacy of topical menthol was evaluated in 24 patients. Eighteen patients (75%) showed over 10% decrease of NRS, and 12 patients (50%) showed over 30% decrease of NRS. Median scores of NRS of baseline, 4 and 8weeks were 4.3, 4.1 and3.6 in hands (p = n.s.; paired t test); 5.4, 4.9 and 4.4 in feet respectively (p = 0.03; paired t test). In modified PNS that assessed the severity of neurological symptoms and functional disabilities caused by CIPN, a decrease of score was observed in 19 of 24 patients (79.2%).


Topical menthol was well tolerated and demonstrated significant therapeutic response for CIPN.


All authors have declared no conflicts of interest.