Abstract
Objective:To compare the Ki-67 index of endometrial cancer cells before and after treatment between the metformin and placebo group in women with endometrial cancer (EC). Methods:This study was a randomized, double-blind, placebo-controlled trial conducting in non-diabetic women who diagnosed with endometrioid EC and had a schedule for elective surgical staging at Rajavithi Hospital between August 2018 and June 2019. Tissue specimens were obtained via endometrial curettage at the time of initial diagnosis (pre-treatment) and hysterectomy (post-treatment) to assess the value of the Ki-67 index by immunochemistry. Patients were randomly assigned into 2 groups: metformin and placebo group. Metformin 850 mg or placebo 1 tab were administered once daily for at least 7 days, starting on the first morning after recruitment until one day before surgery. Baseline characteristics (e.g., age, body mass index, co-morbidities) including surgical and pathological characteristics were recorded. The metabolic effect of metformin was also evaluated by a recording of fasting blood sugar, HbA1C and potential adverse events including nausea, vomiting, dizziness, and hypoglycemic symptom. Results:A total of 49 EC patients were included in this study. Twenty-five patients were assigned to the metformin group and 24 patients were assigned to the placebo group. Baseline demographic, surgical, and pathological characteristics between the 2 groups were similar. Metformin significantly changed the Ki-67 index relative to placebo, with a mean decrease of 23.3% (p=0.001) and a mean proportional decrease of 39.1% (p=0.006) before and after treatment. Additionally, no significant differences were detected in metabolic effects and adverse events between the metformin and the placebo groups. Conclusion:Short-term treatment with an oral metformin significantly reduced a proliferative marker Ki-67 index in women with endometrioid EC awaiting surgical staging. This study supports the biological effect of metformin in EC and potential applications in the adjuvant treatment in EC patients.
Highlights
Endometrial cancer (EC) is the most common gynecologic malignant tumor of the female reproductive tract
Because one patient denied for the surgery after the process of randomization, 50 patients made up the per-protocol population with 25 patients in the metformin group and 24 patients in the placebo group
There was no statistical difference in the baseline levels of Ki-67 expression among patients who were assigned to the metformin and the placebo group
Summary
Endometrial cancer (EC) is the most common gynecologic malignant tumor of the female reproductive tract. EC is fairly common, but the number of new cases appears to be on a rising trend and becomes the second rank of female genital tract cancer after breast cancer. The majority of EC cases are diagnosed at an early stage and have a relatively good survival rate with the 5-year survival rate for local diseases of 95%. Women diagnosed with advanced-stage or recurrence disease have a very poor prognosis with a 5-year survival rate of below 50% (SEER, 2019). The increasing incidence of EC has been attributed to various factors, including obesity, diabetes, reproductive factors, and menopausal hormonal therapy that led to unopposed estrogen stimulation which is a principle fundamental for development of EC (Duncan et al, 2012). The research of novel therapeutic targets which target glucose metabolism and insulin resistance, such as metformin, as a role of treatment of EC is challenging for combat the increasing EC burden
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