Fatemi Shandiz Ashkan, Karimi Gholamreza, Dayyani Mahdiyeh, Hosseini Sare, Elyasi Sepideh
Department of Clinical Pharmacy, Faculty of Pharmacy, University of Medical Sciences, Mashhad, Iran.
Cancer Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
J Oncol Pharm Pract. 2024 Aug 7:10781552241268778. doi: 10.1177/10781552241268778.
Chemotherapy-induced hepatotoxicity is a common complication in breast cancer patients, especially with doxorubicin-containing regimens. Liver enzyme abnormality is reported in 34.8% of patients undergoing AC-T regimen and fatty liver is reported in 30% to 50% of cases. Antioxidant and anti-inflammatory properties of silymarin, a polyphenolic flavonoid extract derived from , may be useful in preventing chemotherapy-induced hepatotoxicity. This study evaluated the effect of oral silymarin for preventing doxorubicin induced hepatotoxicity in non-metastatic breast cancer patients.
In this triple-blind, placebo-controlled clinical trial, 50 patients with non-metastatic breast cancer were assigned to receive either 140 mg silymarin tablets or the placebo three times daily for 63 days and were evaluated for liver function test before the study and at the end of each chemotherapy cycle (every 3 weeks) for 4 cycles. In addition, an ultrasonography assessment was performed upon entry and the end of the study.
Based on ultrasonography, the fatty liver grade was significantly higher in the placebo group at the end of the study. Moreover, the serum levels of aspartate aminotransferase ( = 0.015) and alkaline phosphatase ( = 0.004) at 6-week intervals, and the serum level of alkaline phosphatase ( = 0.002) at 9-week intervals were significantly lower in the silymarin group.
Oral formulation of silymarin 420 mg/day for 63 days significantly prevented hepatotoxicity caused by doxorubicin in patients with non-metastatic breast cancer mostly based on liver ultrasonography but not laboratory parameters. Further investigations are suggested on different doses, durations and formulations of silymarin, particularly nano-formulations for increasing its oral bioavailability.
化疗引起的肝毒性是乳腺癌患者常见的并发症，尤其是在使用含阿霉素的治疗方案时。据报道，接受AC-T方案治疗的患者中有34.8%出现肝酶异常，30%至50%的病例出现脂肪肝。水飞蓟宾是一种从[来源未提及]提取的多酚类黄酮提取物，具有抗氧化和抗炎特性，可能有助于预防化疗引起的肝毒性。本研究评估了口服水飞蓟宾对非转移性乳腺癌患者预防阿霉素引起的肝毒性的效果。
在这项三盲、安慰剂对照的临床试验中，50例非转移性乳腺癌患者被分配接受每日三次、每次140毫克水飞蓟宾片或安慰剂，持续63天，并在研究前以及每个化疗周期结束时（每3周）进行4个周期的肝功能测试评估。此外，在研究开始时和结束时进行超声检查评估。
根据超声检查，研究结束时安慰剂组的脂肪肝分级显著更高。此外，水飞蓟宾组在6周间隔时的天冬氨酸转氨酶（P = 0.015）和碱性磷酸酶水平，以及在9周间隔时的碱性磷酸酶血清水平（P = 0.002）显著更低。
对于非转移性乳腺癌患者，每天口服420毫克水飞蓟宾、持续63天，主要基于肝脏超声检查而非实验室参数，显著预防了阿霉素引起的肝毒性。建议对水飞蓟宾的不同剂量、疗程和制剂，特别是纳米制剂进行进一步研究，以提高其口服生物利用度。
