Mahran Samah E, Salem Salem Eid, Sabry Nirmeen A, Farid Samar F
Department of Clinical Pharmacy, Faculty of Pharmacy, Cairo University, Kasr El-Aini St, P. O. Box: 11562, Cairo, Egypt.
Department of Medical Oncology, National Cancer Institute, Cairo University, Cairo, Egypt.
Int Urol Nephrol. 2025 May 3. doi: 10.1007/s11255-025-04505-2.
Cisplatin-based combination chemotherapy is the mainstay treatment strategy in various forms of carcinomas and sarcomas. However, its dosage and therapeutic efficacy are significantly limited by its nephrotoxicity. Based on metformin renal benefits in different studies, the study aims to determine safety and the potential nephroprotective effect of metformin when used with cisplatin in patients with bladder cancer.
This was a prospective, randomized, parallel, controlled, open-label study in which 78 chemotherapy naïve bladder cancer patients aged 18-65 years and would receive gemcitabine/cisplatin regimen were selected and randomly assigned to treatment or control group in 1:1 allocation. Both groups were receiving cisplatin standard-of-care regimen, whereas metformin (500 mg, twice daily) was added to the treatment group's regimen only. Patients were prospectively followed up for four cycles of gemcitabine/cisplatin with assessment of renal function tests, serum neutrophil gelatinase-associated lipocalin (NGAL), cystatin-c, and metformin's adverse effects.
Serum creatinine, serum NGAL, and cystatin-C significantly increased in the control group only (P < 0.001). Estimated glomerular filtration rate (eGFR) significantly declines in the control group only (P < 0.001). On the contrary, serum NGAL significantly improved in the treatment group (P = 0.02) with stable and normal mean value of serum creatinine, eGFR, and cystatin-C without a concomitant significant increase in adverse events, such as hypoglycemia, gastrointestinal symptoms, or weight loss compared to the control group.
Metformin prevented renal damage and deterioration in kidney function in cisplatin-treated patients. Therefore, it is a promising agent in reducing cisplatin-induced nephrotoxicity. The study was registered in ClinicalTrials.gov on December, 16, 2023, Identifier Number NCT06215976.
基于顺铂的联合化疗是各种形式的癌和肉瘤的主要治疗策略。然而，其剂量和治疗效果受到其肾毒性的显著限制。基于不同研究中二甲双胍对肾脏的益处，本研究旨在确定二甲双胍与顺铂联合用于膀胱癌患者时的安全性和潜在的肾保护作用。
这是一项前瞻性、随机、平行、对照、开放标签研究，选取78例年龄在18至65岁之间、未接受过化疗且将接受吉西他滨/顺铂方案的膀胱癌患者，按1:1比例随机分配至治疗组或对照组。两组均接受顺铂标准治疗方案，而仅在治疗组的方案中添加二甲双胍（500毫克，每日两次）。对患者进行前瞻性随访，观察四个周期的吉西他滨/顺铂治疗情况，评估肾功能测试、血清中性粒细胞明胶酶相关脂质运载蛋白（NGAL）、胱抑素-C以及二甲双胍的不良反应。
仅对照组的血清肌酐、血清NGAL和胱抑素-C显著升高（P＜0.001）。仅对照组的估算肾小球滤过率（eGFR）显著下降（P＜0.001）。相反，治疗组的血清NGAL显著改善（P = 0.02），血清肌酐、eGFR和胱抑素-C的平均值稳定且正常，与对照组相比，低血糖、胃肠道症状或体重减轻等不良事件没有同时显著增加。
二甲双胍可预防顺铂治疗患者的肾损伤和肾功能恶化。因此，它是一种有前景的减轻顺铂诱导肾毒性的药物。该研究于2023年12月16日在ClinicalTrials.gov注册，标识符为NCT06215976。
