Treatment of chemotherapy-induced peripheral neuropathy (CIPN) with topical menthol: A phase I study

D. J. Storey, Lesley Colvin, A. C. Scott, D. Boyle, L. Green, A. P. Jones

Research output: Contribution to journalArticlepeer-review


Background: CIPN is a common dose-limiting toxicity. Mostly symptoms resolve several months post-treatment, but a significant proportion of patients are left with long-term pain and disability which is difficult to treat. The available systemic agents have limited efficacy, cause significant side effects and take several weeks/months to work. Based on preclinical work showing marked analgesic effects of topical transient receptor potential melastatin (TRPM8) receptor activators in neuropathic pain (Proudfoot, Curr Biol 2006;16;1591-1605) we conducted a phase I study of topical menthol.

Methods: 22 patients with long-term CIPN a median of 17 months (range 2 to 35) post-treatment with bortezomib (n=2), carboplatin (n=1), docetaxel (n=2), cisplatin (n=3), and oxaliplatin (n=14) applied 1% topical menthol, twice daily to affected areas and skin overlying the corresponding dorsal root ganglia. At baseline, 2 and 6 weeks, patients completed: Brief Pain Inventory (BPI–measures pain severity and interference with function), Hospital Anxiety and Depression Scale (HADS) and Pain Catastrophizing Scale (PCS). Responders and partial responders were defined as 30% and 10-20% reduction in mean BPI respectively.

Results: At 2 weeks, 36%(8/22) were responders, 14%(3/22) were partial responders and 50%(11/22) were non-responders. This further improved by 6 weeks: 47%(9/19) were responders 21%(4/19) were partial responders and 32%(6/19) were non-responders. 3 patients discontinued treatment after 2 weeks: 1 had progressive disease; 2 had difficulty applying the cream. Between baseline and 6 weeks, distress decreased in responders [mean HADS 10.9 (SD 6.2) to 7.7 (6.1)] but not in partial responders [6.5 (2.9) to 7.0 (4.5)] or non-responders [17.2 (4.9) to 17.2 (7.1)]. Catastrophizing decreased in all groups but most markedly in responders [mean 16.3 (SD6.2) to 7.7 (8.2)]; partial responders from 7.3 (3.1) to 5.0 (3.9); non-responders from 22.0 (15.2) to 18.4 (12.5).

Conclusions: Two thirds of patients with long-term CIPN experienced an improvement in pain and function with topical menthol. This novel treatment appears to be well tolerated, have minimal side effects, works relatively quickly and warrants further study.
Original languageEnglish
Pages (from-to)9129
Number of pages1
JournalJournal of Clinical Oncology
Issue number15 Suppl.
Publication statusPublished - 20 May 2010


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