Gewandter, J.S., Mohile, S.G., Heckler, C.E., Ryan, J.L., Kirshner, J.J., Flynn, P.J., . . . Morrow, G.R. (2014). A phase III randomized, placebo-controlled study of topical amitriptyline and ketamine for chemotherapy-induced peripheral neuropathy (CIPN): A University of Rochester CCOP study of 462 cancer survivors. Supportive Care in Cancer, 22, 1807–1814.
To determine the effectiveness and safety of the topical application of a combined 2% ketamine and 4% amitriptyline (KA) cream for reduction of chemotherapy-induced peripheral neuropathy (CIPN) in patients who have completed chemotherapy
One week prior to enrollment, subjects completed a seven-day daily pain, numbness, and tingling diary over the past 24 hours. Subjects answered the question for any of the three symptoms in either their hands or feet. At enrollment, subjects were instructed to use a measuring device for application of 4 g of either KA or placebo cream twice daily to each area of hands or feet with any pain, numbness, or tingling. The seven-day daily pain, numbness, and tingling diary for pain over the past 24 hours, by numeric rating scale (NRS), was completed at three and six weeks after enrollment. A secondary analysis for pain using NRS was done at baseline, three, and six weeks.
No therapeutic effect was observed with the application of KA cream to the affected areas on hands or feet for reduction of pain, numbness, and tingling (p = 0.363). Secondary analysis for pain alone did not show a statistically significant difference between groups comparing means at 95% CI (KA cream, 4.64; placebo, 4.68). Patients in the treatment regimen group of prior taxanes, regardless of receiving study treatment with either KA or placebo, reported a reduction in pain, numbness, and tingling at six weeks (p = 0.042). No statistically significant adverse events were reported for the KA treatment group compared to the placebo group.
This study showed no therapeutic benefit for the topical application of KA cream for CIPN.
Further studies need to be done to investigate if any combination or separate topical compound targeting specific nociceptive pathways has a therapeutic benefit for CIPN.