Effect of melatonin on taxane-induced neuropathy in breast cancer patients

Abstract

19640 Background: Neurotoxicity caused by taxane chemotherapies(CT) can be dose limiting and can cause a decrease in quality of life. Melatonin has been evaluated for its use in decreasing adverse reactions of CT. Preclinical data suggests that melatonin has neuroprotective capability. The objective of this study is to determine if melatonin will decrease the incidence and severity of taxane-related neuropathy. Methods: Fifty patients beginning CT for any stage of breast cancer with paclitaxel, albumin-bound paclitaxel, or docetaxel will be enrolled. Patients should have no underlying neuropathy. Melatonin is given at 21 mg at bedtime on Day 1 and continued for 28 days after the last taxane dose. Every 28 days, neuropathy is assessed using the NCI-CTC 3.0 scale and possible side effects of melatonin are evaluated. Quality of life (QOL) is analyzed using the FACT-Taxane QOL assessment. Outcomes analyzed included the incidence and severity of neuropathy, and changes in QOL. Results: Currently 17 patients have been enrolled with 12 having completed taxaneCT and melatonin. Five have withdrawn due to non-medical reasons and were evaluated for toxicities. The mean age is 49 years (range 36–67 years). The end of study FACT-Taxane score was available for 11 of the 12 patients, with an average score of 135 (range 106–168). The average baseline QOL score was 131 (range 99–148). The average change in QOL score was +4. Eleven have completed paclitaxel with an average dose of 862 mg/m2 (range 525–1620 mg/m2). One patient received docetaxel t 450 mg/m2. Five patients self- reported adverse effects including night-time sedation (2), hot flashes (1), headache (1), constipation (1), nail darkening (1), and fatigue (1). Neuropathy distribution was as follows : 50 % (6) of patients had grade 0, 33% (4) grade 1, and 16% (2) grade 2 neuropathy. The mean change in neuropathy score was +0.67. Conclusion: Melatonin appears promising as a neuroprotective agent in patients receiving taxane-based chemotherapy. No patient developed grade 3 or 4 neuropathy compared to historical controls of 22–33%. Fifty percent of patients treated with melatonin while on taxane CT developed no neuropathy, and those who did, had grade 1 or 2 neuropathy.QOL was maintained. Melatonin's neuroprotective effect should be further evaluated. No significant financial relationships to disclose.