Department of Pharmacology and Toxicology, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt.
Department of Clinical Pharmacy and Pharmacy Practice, Faculty of Pharmacy, Damanhour University, Damanhour, Egypt.
Drug Saf. 2023 Jun;46(6):587-599. doi: 10.1007/s40264-023-01305-4. Epub 2023 May 2.
Breast cancer patients treated with adriamycin-cyclophosphamide plus paclitaxel (AC-T) are often challenged with serious adverse effects for which no effective therapies are available. Here, we investigated whether metformin, an antidiabetic drug with additional pleiotropic effects could favourably offset AC-T induced toxicities.
Seventy non-diabetic breast cancer patients were randomised to receive either AC-T (adriamycin 60 mg/m + cyclophosphamide 600 mg/m × 4 cycles Q21 days, followed by weekly paclitaxel 80 mg/m × 12 cycles) alone or AC-T plus metformin (1700 mg/day). Patients were assessed regularly after each cycle to record the incidence and severity of adverse events based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 5.0. Moreover, baseline echocardiography and ultrasonography were done and repeated after the end of neoadjuvant therapy.
Addition of metformin to AC-T resulted in significantly less incidence and severity of peripheral neuropathy, oral mucositis, and fatigue (p < 0.05) compared to control arm. Moreover, the left ventricular ejection fraction (LVEF%) in the control arm dropped from a mean of 66.69 ± 4.57 to 62.2 ± 5.22% (p = 0.0004) versus a preserved cardiac function in the metformin arm (64.87 ± 4.84 to 65.94 ± 3.44%, p = 0.2667). Furthermore, fatty liver incidence was significantly lower in metformin compared with control arm (8.33% vs 51.85%, p = 0.001). By contrast, haematological disturbances caused by AC-T were preserved after concurrent metformin administration (p > 0.05).
Metformin offers a therapeutic opportunity for controlling toxicities caused by neoadjuvant chemotherapy in non-diabetic breast cancer patients.
This randomised controlled trial was registered on November 20, 2019 in ClinicalTrials.gov under registration number: NCT04170465.
接受阿霉素-环磷酰胺加紫杉醇（AC-T）治疗的乳腺癌患者常面临严重的不良反应，而目前尚无有效的治疗方法。本研究旨在探讨一种具有额外多效性作用的抗糖尿病药物二甲双胍是否可以有利地减轻 AC-T 诱导的毒性。
70 例非糖尿病乳腺癌患者被随机分为两组，分别接受 AC-T（阿霉素 60mg/m+环磷酰胺 600mg/m×4 周期，每 21 天 1 次，随后每周紫杉醇 80mg/m×12 周期）单药治疗或 AC-T+二甲双胍（1700mg/天）治疗。在每个周期后，患者接受定期评估，根据美国国立癌症研究所不良事件通用术语标准（NCI-CTCAE）第 5.0 版记录不良事件的发生率和严重程度。此外，在新辅助治疗结束后，对基线超声心动图和超声进行检查并重复检查。
与对照组相比，AC-T+二甲双胍组的周围神经病变、口腔黏膜炎和疲劳的发生率和严重程度显著降低（p<0.05）。此外，对照组的左心室射血分数（LVEF%）从平均 66.69±4.57%降至 62.2±5.22%（p=0.0004），而二甲双胍组的心脏功能保持不变（64.87±4.84%至 65.94±3.44%，p=0.2667）。此外，二甲双胍组的脂肪肝发生率明显低于对照组（8.33%比 51.85%，p=0.001）。相反，AC-T 引起的血液学紊乱在同时使用二甲双胍后得到保留（p>0.05）。
二甲双胍为非糖尿病乳腺癌患者新辅助化疗毒性的控制提供了治疗机会。
本随机对照试验于 2019 年 11 月 20 日在 ClinicalTrials.gov 注册，注册号为 NCT04170465。
