Evaluation of oral silymarin formulation efficacy in prevention of doxorubicin induced hepatotoxicity in patients with non-metastatic breast cancer.
- 2024-08-07
- Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners 31(6)
- Ashkan Fatemi Shandiz
- Gholamreza Karimi
- Mahdiyeh Dayyani
- Sare Hosseini
- Sepideh Elyasi
- PubMed: 39110237
- DOI: 10.1177/10781552241268778
Study Design
- Type
- Randomized Controlled Trial (RCT)
- Sample size
- n = 50
- Population
- 50 patients with non-metastatic breast cancer
- Methods
- Triple-blind, placebo-controlled clinical trial; patients received either 140 mg silymarin tablets or placebo three times daily for 63 days; evaluated for liver function test before the study and at the end of each chemotherapy cycle (every 3 weeks) for 4 cycles; ultrasonography assessment upon entry and at the end of the study
- Blinding
- Triple-blind
- Duration
- 63 days
- Funding
- Unclear
IntroductionChemotherapy-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 Silybum marianum, 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.MethodsIn 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.ResultsBased 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 (p = 0.015) and alkaline phosphatase (p = 0.004) at 6-week intervals, and the serum level of alkaline phosphatase (p = 0.002) at 9-week intervals were significantly lower in the silymarin group.ConclusionOral 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.
Research Insights
the serum level of alkaline phosphatase (p = 0.004) at 6-week intervals, and the serum level of alkaline phosphatase (p = 0.002) at 9-week intervals were significantly lower in the silymarin group.
- Effect
- Beneficial
- Effect size
- Small
- Dose
- 420 mg/day
the serum levels of aspartate aminotransferase (p = 0.015) ... at 6-week intervals ... were significantly lower in the silymarin group.
- Effect
- Beneficial
- Effect size
- Small
- Dose
- 420 mg/day
Based on ultrasonography, the fatty liver grade was significantly higher in the placebo group at the end of the study.
- Effect
- Beneficial
- Effect size
- Small
- Dose
- 420 mg/day