Usmani Nawaid, Ghosh Sunita, Sanghera Karan P, Ong Aldrich D, Koul Rashmi, Dubey Arbind, Ahmed Shahida, Quon Harvey, Yee Don, Parliament Matthew, Sivananthan Gokulan, Hunter William, Danielson Brita, Rowe Lindsay, McDonald Megan, Kim Julian O
Division of Radiation Oncology, Cross Cancer Institute, Edmonton, Alberta, Canada.
Division of Experimental Oncology, Cross Cancer Institute, Edmonton, Alberta, Canada.
Int J Radiat Oncol Biol Phys. 2023 Feb 1;115(2):317-326. doi: 10.1016/j.ijrobp.2022.07.035. Epub 2022 Jul 28.
Patients with prostate cancer undergoing treatment with radical radiation therapy (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 effect of metformin versus placebo to blunt the adverse effects 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 (18-36 months) in a 1:1 ratio to receive metformin 500 mg by mouth 3 times a day (for 30-36 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 among men who received metformin compared with placebo at 5 months (-1.80 kg, P = .038), but was not significant with longer follow-up (1 year: +0.16 kg, P = .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) versus +1.46 cm (metformin), P = .336). Low-density lipoprotein (LDL) cholesterol was lower in the metformin arm (-0.32 mmol/L) compared with the placebo arm (-0.03 mmol/L) at 5 months (P = .022), but these differences were not significant with longer follow-up (1 year: -0.17 mmol/L vs -0.19 mmol/L, P = .896). There were no differences in HbA1C, triglyceride, high-density lipoprotein (HDL) cholesterol, and total cholesterol by study arm.
Men receiving radical RT and ADT gained weight and had increases in waist circumference over time that metformin did not significantly mitigate. Although this study did not observe any preventive effect 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 antineoplastic effects.
接受根治性放射治疗（RT）加雄激素剥夺治疗（ADT）的前列腺癌患者会出现一系列与性腺功能减退相关的有害代谢和人体测量学变化，这些变化与发病率和死亡率增加有关。我们评估了二甲双胍与安慰剂对减轻ADT对体重、腰围和其他代谢参数的不良影响的效果。
这项2期、多中心、随机对照试验（RCT）将血糖正常、患有局部晚期前列腺癌且接受根治性RT和ADT（18 - 36个月）的男性按1:1比例随机分组，一组每天口服3次500毫克二甲双胍（共30 - 36个月），另一组服用相同的安慰剂。
2015年12月至2019年10月，83名男性被随机分组，中位随访时间为23个月。该队列的基线平均体重指数（BMI）为30.2（范围22.2 - 52.5）。在5个月时，接受二甲双胍治疗的男性相对于基线的平均体重变化低于接受安慰剂的男性（-1.80千克，P = 0.038），但随访时间延长后差异无统计学意义（1年时：+0.16千克，P = 0.874）。虽然在两个研究组中接受ADT的参与者腰围均增加，但二甲双胍并未显著降低这些变化（1年时：安慰剂组增加2.79厘米，二甲双胍组增加1.46厘米，P = 0.336）。在5个月时，二甲双胍组的低密度脂蛋白（LDL）胆固醇低于安慰剂组（-0.32毫摩尔/升 vs -0.03毫摩尔/升，P = 0.022），但随访时间延长后这些差异无统计学意义（1年时：-0.17毫摩尔/升 vs -0.19毫摩尔/升，P = 0.896）。按研究组划分，糖化血红蛋白、甘油三酯、高密度脂蛋白（HDL）胆固醇和总胆固醇无差异。
接受根治性RT和ADT的男性体重增加，腰围随时间增加，二甲双胍并未显著减轻这些变化。尽管本研究未观察到二甲双胍对ADT的人体测量学和代谢并发症有任何预防作用，但二甲双胍仍在该患者群体的3期RCT中进行研究，以评估其潜在的抗肿瘤作用。
