Diani Kartini1, Akmal Taher2, Sonar Soni Panigoro1, Rianto Setiabudy3, Sri Widia Jusman4, Sofia Mubarika Haryana5, Abdullah Murdani6, Primariadewi Rustamadji7, Adlina Karisyah1, Sani Hadiyan Rasyid1
1Oncology Division, Department of Surgery, Cipto Mangunkusumo General Hospital, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
2Department of Urology, Cipto Mangunkusumo General Hospital, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
3Department of Pharmacology and Therapeutics, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
4Department of Biochemistry and Molecular Genetics, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
5Department of Histology and Cell Biology, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia
6Division of Gastroenterology and Hepatology, Department of Internal Medicine, Cipto Mangunkusumo General Hospital, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
7Department of Pathological Anatomy, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
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.
Keywords: Chemoresistance, hypoxia-inducible factor-1α, melatonin, oral squamous cell carcinoma