Metformin for Prevention of Anthropometric & Metabolic Complications of Androgen Deprivation Therapy in Prostate Cancer Patients Receiving Radical Radiotherapy: A Phase II Randomized Controlled Trial.

Prostate cancer patients undergoing treatment with radical radiotherapy (RT) plus androgen deprivation therapy (ADT) experience a constellation of deleterious metabolic and anthropometric changes related to hypogonadism that are associated with increased morbidity and mortality. We assessed the impact of metformin versus placebo to blunt the adverse impact of ADT on body weight, waist circumference, and other metabolic parameters.

This phase 2, multicenter, randomized controlled trial (RCT) randomized normoglycemic men with locally advanced prostate cancer receiving radical RT and ADT (18 to 36 months) in a 1:1 ratio to receive Metformin 500mg by mouth three times a day (for 30 to 36 months) versus identical placebo.

From December 2015 to October 2019, 83 men were randomized with median follow-up of 23 months. Baseline mean body mass Index (BMI) of the cohort was 30.2 (range 22.2-52.5). Change in mean weight relative to baseline was lower amongst men who received metformin compared to placebo at 5 months (-1.80 kg, p=0.038), but was not significant with longer follow-up (1 year: +0.16 kg, p=0.874). Although participants on ADT had increases in waist circumference in both study arms, metformin did not significantly reduce these changes (1 year: +2.79 cm (placebo) vs. +1.46 cm (metformin), p=0.336). LDL cholesterol was lower in the metformin arm (-0.32 mmol/L) when compared to the placebo arm (-0.03 mmol/L) at 5 months (p=0.022), but these differences were not significant with longer follow-up (1 year: -0.17 mmol/L vs -0.19 mmol/L, p=0.896). There were no differences in HbA1C, triglyceride, HDL, and total cholesterol by study arm.

Men receiving radical RT and ADT gained weight and had increases in waist circumference over time, which metformin did not significantly mitigate. Although this study did not observe any preventative impact of metformin on the anthropometric and metabolic complications of ADT, metformin continues to be studied in phase 3 RCTs in this patient population to assess its potential anti-neoplastic effects.

International journal of radiation oncology, biology, physics. 2022 Jul 27 [Epub ahead of print]

Nawaid Usmani, Sunita Ghosh, Karan P Sanghera, Aldrich D Ong, Rashmi Koul, Arbind Dubey, Shahida Ahmed, Harvey Quon, Don Yee, Matthew Parliament, Gokulan Sivananthan, William Hunter, Brita Danielson, Lindsay Rowe, Megan McDonald, Julian O Kim

Division of Radiation Oncology, Cross Cancer Institute, Edmonton, Alberta, Canada., Division of Experimental Oncology, Cross Cancer Institute, Edmonton, Alberta, Canada., Section of Radiation Oncology, Dept of Radiology, Max Rady Faculty of Heath Sciences, University of Manitoba, Winnipeg, Manitoba, Canada., Division of Radiation Oncology, Tom Baker Cancer Center, University of Calgary, Calgary, Alberta, Canada., Section of Radiation Oncology, Dept of Radiology, Max Rady Faculty of Heath Sciences, University of Manitoba, Winnipeg, Manitoba, Canada; Western Manitoba Cancer Centre, Brandon, Manitoba, Canada., Section of Radiation Oncology, Dept of Radiology, Max Rady Faculty of Heath Sciences, University of Manitoba, Winnipeg, Manitoba, Canada; CancerCare Manitoba Research Institute, Winnipeg, Manitoba, Canada. Electronic address: .

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