The Possible Anticancer Effect of Silymarin in Patients With Metastatic Colorectal Cancer Receiving Chemotherapy.
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 64
- 试验地点
- 1
- 主要终点
- The change between groups in response rate (RECIST)
研究概览
简要总结
this work is aim to assess the antitumor effect of silymarin in patients with metastatic colorectal cancer receiving chemotherapy with or without target therapy (Bevacizumab).
详细描述
Colorectal cancer (CRC) ranks as the third most common cancer globally and second in terms of mortality . Although CRC incidence rates are higher in high-income compared with low-to-middle-income countries (LMICs), mortality is higher in LMICs.
Extensive research within the last decade has shown that silymarin can suppress the proliferation of a variety of tumor cells; this is accomplished through cell cycle arrest at the G1/S-phase, induction of cyclin-dependent kinase inhibitors, down-regulation of anti- apoptotic gene products, inhibition of cell-survival kinases and inhibition of inflammatory transcription factors (e.g., Nuclear Factor- kappa B) through suppression of Nuclear Factor- kappa B-regulated gene products, including Cyclooxygenase-2, Lipoxygenase, Tumor necrosis factor and Interleukin-1. Silymarin can also down-regulate gene products involved in the proliferation of tumor cells (Epidermal Growth Factor Receptor, Cyclooxygenase-2), invasion (Matrix metallopeptidase 9), angiogenesis (Vascular Endothelial growth Factor) and metastasis (adhesion molecules). Silymarin was reported to alter the expression of apoptosis-related proteins including BCL2 associated X protein to induce apoptosis in human gastric cancer cells in a concentration-dependent manner. Silymarin has also been shown to sensitize tumors to chemotherapeutic agents through down-regulation of the Multidrug resistance protein and other mechanisms. In addition to its chemo-preventive effects, silymarin exhibits antitumor activity against human tumors in rodents. so we aim to assess the antitumor activity of silymarin in metastatic colorectal cancer patients receiving chemotherapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •- Patients with histologically and/or radiologically confirmed diagnosis of metastatic colorectal carcinoma.
- •Patients who received FOLFOX or XELOX as first line chemotherapy
- •Both genders.
- •Age ≥18 years old.
- •Performance status 0-1 according to the Eastern Cooperative Oncology Group (ECOG).
- •Patients with adequate hematologic parameters (white blood cell count
- •≥3000/mm3, granulocytes ≥1500/mm3, platelets ≥100,000/mm3, hemoglobin ≥ 8 gm/l).
- •Patients with adequate renal functions (serum creatinine ≤1.5 mg/dL).
- •Patients with adequate hepatic functions (bilirubin ≤1.5 mg/dL or albumin ≥3 g/dL).
排除标准
- •- Patients with active liver diseases (chronic viral hepatitis, autoimmune hepatitis, alcoholic hepatitis, Wilson's disease, hemochromatosis, or cirrhosis).
- •Patients with a history of other malignancy.
- •Patients with brain metastasis.
- •Patients with active infection.
- •Patients with RAS wild type cancer.
- •Patients on chronic use of corticosteroids.
研究组 & 干预措施
Silymarin group
Group II: (Silymarin group ; n=32) which will receive FOLFIRI regimen (5-flourouracil, leucovorin, irinotecan) or XELIRI (Capecitabine and irinotecan) with or without target therapy (Bevacizumab). plus silymarin 140 mg once daily.
干预措施: Silymarin (Drug)
结局指标
主要结局
The change between groups in response rate (RECIST)
时间窗: At baseline, pre-intervention and at the end of last chemotherapy cycle ( 3 months from the beginning ) patients will recieve either Folfiri 6 cycles ( each cycle is 14 days) or Xeliri 4 cycles ( each cycle is 21 days)
Tumor response is characterized by both objective response rates (ORR=Complete response + partial response) and disease control rate (DCR= complete response + partial response + stable disease). In addition, complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) will be evaluated. Follow-up for one year will be carried out to determine progression free survival (PFS) and the overall survival (OS) or one year survival.
次要结局
- Changes in serum levels of the measured biological marker serum carcinoembryonic antigen in ng/ ml or Carbohydrate antigen 19-9 in U/ml.(3 Months. At baseline( pre-intervention )and at the end of last chemotherapy cycle ( 3 months from the beginning ) patients will recieve either Folfiri 6 cycles ( each cycle is 14 days) or Xeliri 4 cycles ( each cycle is 21 days).)
- Changes in serum levels of the measured biological marker serum Bax protein in ng/ml.(3 Months. At baseline( pre-intervention )and at the end of last chemotherapy cycle ( 3 months from the beginning ) patients will recieve either Folfiri 6 cycles ( each cycle is 14 days) or Xeliri 4 cycles ( each cycle is 21 days).)
- Changes in serum levels of the measured biological marker serum permeability glycoprotein in ng/ml(3 Months. At baseline( pre-intervention )and at the end of last chemotherapy cycle ( 3 months from the beginning ) patients will recieve either Folfiri 6 cycles ( each cycle is 14 days) or Xeliri 4 cycles ( each cycle is 21 days).)
- Changes in serum levels of the measured biological marker serum vascular endothelial growth factor in pg/ml.(3 Months. At baseline( pre-intervention )and at the end of last chemotherapy cycle ( 3 months from the beginning ) patients will recieve either Folfiri 6 cycles ( each cycle is 14 days) or Xeliri 4 cycles ( each cycle is 21 days).)
研究者
Shimaa Yassin Abdelghafaar Mohamed
principal Investigator
Tanta University