The antitumor effect of melatonin (MLT) and metformin (MTF) has been shown in vitro/in vivo. According to recent data both MLT and MTF may become a new drug which can be used in combination with standard cancer treatment, however, this hypothesis needs confirmation in clinical trials.
A total of 54 patients with estrogen receptor-positive locally advanced breast cancer (ER+BC) were included in the study of MLT or MTF efficiency in combination with toremifene (TOR) neoadjuvant hormone therapy (clinicalTrials.gov NCT02506790). The average patients’ age was 68 years. All patients had no history of diabetes mellitus. All patients were randomized for 1:1:1 ratio. The first group (n = 19) received 120 mg of oral TOR daily, the second one (n = 16) received TOR in combination with 3 mg overnight dose of oral MLT, the third group (n = 19) received TOR in combination with oral MTF (850 mg twice a day). For all patient groups the hormone therapy duration was 4 months, then surgery was performed.
An objective response rate for three studied groups was 31.6%, 86.7%. and 47.3% accordingly. Adding MLT to TOR lead to significant increase in response rate compared to TOR monotherapy group (χ2 = 10.32, p=0.001). The decrease in Ki67 expression in TOR group was observed in 42%, TOR+ MLT group in 56%, and TOR+MTF group in 74% of patients. According to multivariate analysis of results the TOR combination with MTF leads to 4.2-fold higher Ki-67 expression decrease probability compared to TOR group (OR 4.23 [95% CI 1.044-17.139], p=0.043). Also this group is the only one to display a significant correlation (Spearman) between Ki67 expression decrease dynamics and abnormal BMI values (p=0.015). No pathomorphological response (pCR) was observed. Adding MLT or MTF to standard hormone therapy did not lead to decrease in the quality of life (EORTC-QLQ-C30), about 50% of TOR+MLT therapy recipients had better sleep quality.
MLT and MTF showed encouraging results in combination with neoadjuvant hormonotherapy. However, these data require confirmation in larger randomized studies.
Federal State Budget Institution "National Medical Research Center of Oncology na N.N. Petrov" Ministry of Healthcare of Russian Federation.
All authors have declared no conflicts of interest.