B-Y Yang1,2, Y Gulinazi1,2, Y Du3, C-C Ning1,2, Y-L Cheng1,2, W-W Shan1,2, X-Z Luo1,2, H-W Zhang4, Q Zhu5, F-H Ma6, J Liu6, L Sun7, M Yu8, J Guan1,2,9, X-J Chen1,2. 1. Department of Gynaecology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China. 2. Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, China. 3. Department of Clinical Epidemiology, Obstetrics and Gynaecology Hospital, Fudan University, Shanghai, China. 4. Department of Cervical Diseases, Obstetrics and Gynaecology Hospital, Fudan University, Shanghai, China. 5. Department of Pathology, Obstetrics and Gynaecology Hospital, Fudan University, Shanghai, China. 6. Department of Radiology, Obstetrics and Gynaecology Hospital, Fudan University, Shanghai, China. 7. Department of Sonography, Obstetrics and Gynaecology Hospital, Fudan University, Shanghai, China. 8. Shanghai JiAi Genetics and IVF Institute, Obstetrics and Gynaecology Hospital, Fudan University, Shanghai, China. 9. Department of Gynaecology, Campus Virchow Clinic, Charite Medical University of Berlin, corporate member of Free University Berlin, Humboldt-University Berlin, Berlin Institute of Health, Berlin, Germany.
Abstract
OBJECTIVE: To assess the efficacy of metformin in megestrol acetate (MA)-based fertility-sparing treatment for patients with atypical endometrial hyperplasia (AEH) and endometrioid endometrial cancer (EEC). DESIGN: A randomised, single-centre, open-label, controlled trial conducted between October 2013 and December 2017. SETTING: Shanghai OBGYN Hospital of Fudan University, China. POPULATION: A total of 150 patients (18-45 years old) with primary AEH or well-differentiated EEC were randomised into an MA group (n = 74) and an MA plus metformin group (n = 76). METHODS:Patients with AEH or EEC were firstly stratified, then randomised to receive MA (160 mg orally, daily) or MA (160 mg orally, daily) plus metformin (500 mg orally, three times a day). MAIN OUTCOMES AND MEASURES: The primary efficacy parameter was the cumulate complete response (CR) rate within 16 weeks of treatment (16w-CR rate); the secondary efficacy parameters were 30w-CR rate and adverse events. RESULTS: The 16w-CR rate was higher in the metformin plus MA group than in the MA-only group (34.3 versus 20.7%, odds ratio [OR] 2.0, 95% confidence interval [CI] 0.89-4.51, P = 0.09) but the difference was more significant in 102 AEH patients (39.6 versus 20.4%, OR 2.56, 95% CI 1.06-6.21, P = 0.04). This effect of metformin was also significant in non-obese (51.4 versus 24.3%, OR 3.28, 95% CI 1.22-8.84, P = 0.02) and insulin-sensitive (54.8 versus 28.6%, OR 3.04, 95% CI 1.03-8.97, P = 0.04) subgroups of AEH women. No significant result was found in secondary endpoints. CONCLUSION: As a fertility-sparing treatment, metformin plus MA was associated with a higher early CR rate compared with MA alone in AEH patients. TWEETABLE ABSTRACT: For AEH patients, metformin plus MA might be a better fertility-sparing treatment to achieve a higher early CR rate compared with MA alone.
RCT Entities:
OBJECTIVE: To assess the efficacy of metformin in megestrol acetate (MA)-based fertility-sparing treatment for patients with atypical endometrial hyperplasia (AEH) and endometrioid endometrial cancer (EEC). DESIGN: A randomised, single-centre, open-label, controlled trial conducted between October 2013 and December 2017. SETTING: Shanghai OBGYN Hospital of Fudan University, China. POPULATION: A total of 150 patients (18-45 years old) with primary AEH or well-differentiated EEC were randomised into an MA group (n = 74) and an MA plus metformin group (n = 76). METHODS:Patients with AEH or EEC were firstly stratified, then randomised to receive MA (160 mg orally, daily) or MA (160 mg orally, daily) plus metformin (500 mg orally, three times a day). MAIN OUTCOMES AND MEASURES: The primary efficacy parameter was the cumulate complete response (CR) rate within 16 weeks of treatment (16w-CR rate); the secondary efficacy parameters were 30w-CR rate and adverse events. RESULTS: The 16w-CR rate was higher in the metformin plus MA group than in the MA-only group (34.3 versus 20.7%, odds ratio [OR] 2.0, 95% confidence interval [CI] 0.89-4.51, P = 0.09) but the difference was more significant in 102 AEHpatients (39.6 versus 20.4%, OR 2.56, 95% CI 1.06-6.21, P = 0.04). This effect of metformin was also significant in non-obese (51.4 versus 24.3%, OR 3.28, 95% CI 1.22-8.84, P = 0.02) and insulin-sensitive (54.8 versus 28.6%, OR 3.04, 95% CI 1.03-8.97, P = 0.04) subgroups of AEHwomen. No significant result was found in secondary endpoints. CONCLUSION: As a fertility-sparing treatment, metformin plus MA was associated with a higher early CR rate compared with MA alone in AEHpatients. TWEETABLE ABSTRACT: For AEHpatients, metformin plus MA might be a better fertility-sparing treatment to achieve a higher early CR rate compared with MA alone.
Authors: Salvatore Giovanni Vitale; Gaetano Riemma; Jose Carugno; Benito Chiofalo; George Angelos Vilos; Stefano Cianci; Mehmet Sukru Budak; Bernardo Portugal Lasmar; Antonio Raffone; Ilker Kahramanoglu Journal: Transl Cancer Res Date: 2020-12 Impact factor: 1.241