PURPOSEThe purpose of this study is to assess the effect of topical amitriptyline, ketamine, and lidocaine (AKL) on alleviation of neuropathic pain from radiation dermatitis and the feasibility of a randomized trial.MATERIALS AND METHODSEligible subjects had radiation dermatitis with dry or moist desquamation with neuropathic pain and were intolerant or allergic to standard intervention. AKL was applied to painful sites three times a day daily until 2 weeks post-radiotherapy. Subjects were monitored every 2-5 days during radiotherapy and at 2 and 6 weeks after completion of radiotherapy. The University of Washington Neuropathic Pain Scale was used to grade the neuropathic pain before and after use of the interventional gel. Compliance was assessed by asking subjects at each visit how frequently they were using the interventional gel.RESULTSOver a 14-month period, 16 subjects met eligibility criteria. Eighty-two percent of subjects used the AKL as directed. Five subjects (32%) reported fatigue, and three subjects (19%) reported site irritation from the interventional gel. AKL was shown to significantly reduce (p < 0.05) pain intensity, sharpness, burning, sensitivity, itchiness, unpleasantness, deepness, and surfaceness levels on a short-term basis (i.e., between pre-treatment and 30 min post-treatment). AKL was shown to significantly reduce (p < 0.05) burning levels on a long-term basis (i.e., between pre-treatment and 2 weeks post-treatment).CONCLUSIONSAKL was a safe intervention to use with minimal toxicity and good compliance. It significantly reduced several measures of neuropathic pain associated with radiation dermatitis. A larger-scale study would require recruitment from multiple centers.