Effect of Melatonin on Oxaliplatin Induced Neuropathy in Patients Receiving Folfox Chemotherapy Regimens for Stage II–IV Colorectal Cancer: A Randomized, Placebo Controlled, Double Blind Trial

Abstract

Background and Aims

Peripheral neuropathy is a major side effect of oxaliplatin-based chemotherapy. The aim of this placebo-controlled double-blind randomized study was to evaluate the effect of melatonin on prevention of oxaliplatin induced peripheral neuropathy (OXIPN) in patients receiving oxaliplatin for colorectal cancer.

Methods

Patients with stage II–IV colorectal cancer, who were to receive oxaliplatin-based chemotherapy, were enrolled according to the inclusion criteria and randomly assigned to take either melatonin (20 mg/day) or placebo, during chemotherapy and 1 month after. Neuropathy was assessed by several patient- and physician-based reports, including the National Cancer Institute Common Terminology Criteria for Adverse Events scale (NCI-CTCAE), European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Chemotherapy-Induced Peripheral Neuropathy 20 (EORTC QLQ-CIPN20) scale, and oxaliplatin specific scale (OSS).

Results

From a total of 80 selected patients, 54 completed the study and were evaluated for the final analysis. Grade 3 neuropathy measured by NCI-CTCAE and OSS in the melatonin arm was significantly lower than the placebo group. But according to EORTC QLQ-CIPN20 scale, no statistically significant difference was observed between the groups. In addition, melatonin use did not improve patients' quality of life compared with placebo.

Conclusion

Reduction in grade 3 neuropathy based on NCI-CTCAE and OSS can be of great importance, as it is the higher-grade neuropathy that may lead to functional impairment. Given that to date no medication has been approved for prevention of OXIPN and considering the limited number of patients in the present study, conducting a larger clinical trial on the effect of melatonin may lead to beneficial results in this group of patients.

Trial Registration: Study registered (Date: 23 July, 2018) in the Iranian Registry of Clinical Trials (IRCT); IRCT20170326033139N1 (https://www.irct.ir/search/result?query=IRCT20170326033139N1)