Melatonin effect on hypoxia inducible factor-1α and clinical response in patients with oral squamous cell carcinoma receiving neoadjuvant chemotherapy: A randomized controlled trial.

CONTEXT: Chemoresistance is a major issue in patients with locally advanced oral squamous cell carcinoma (OSCC). In this study, we evaluated the effectiveness of melatonin in conjunction with neoadjuvant chemotherapy (NC) on hypoxia-inducible factor-1α (HIF-1α) expression and clinical response in locally advanced OSCC patients.

AIMS: To study the effects of melatonin on HIF-1α expression and its effect on the clinical response of patients with locally advanced OSCC.

SETTINGS AND DESIGN: A randomized controlled trial was conducted, wherein patients were recruited from several hospitals in Jakarta, Indonesia. Patients were randomized into two groups using computerized block randomization.

SUBJECTS AND METHODS: Both groups were given NC, with treatment group receiving melatonin. Outcomes measured in this study were HIF-1α expression from tissue samples and clinical response based on the RECIST 1.1 criteria. Twenty-five patients completed the study protocol and were included in the data analysis.

STATISTICAL ANALYSIS USED: Shapiro-Wilk test was used to test the data normality. For data with normal distribution, we conducted an independent t -test to compare between the two groups. Data with abnormal distribution were analyzed using Mann-Whitney U-test. The mean difference between the two groups was analyzed using Shapiro-Wilk normality test.

RESULTS: Our study showed a significant decrease in HIF-1α expression in the melatonin group compared to the placebo group ( P < 0.05, relative risk 3.08). However, the degree of reduction of HIF-1α expression in the melatonin group did not differ significantly ( P = 0.301).

CONCLUSIONS: Our study showed that melatonin administered at 20 mg/day could reduce the expression of HIF-1α and residual tumor percentage, but did not affect the clinical response in OSCC patients.