Neoplasms

All Conditions

Adenocarcinoma

Antineoplastic Agents

All Drugs and Chemicals

Flavonoid

Herbal and Botanical

Docetaxel

Fluorouracil

Silymarin

Cisplatin

Antioxidants

Tubulin Modulators

Antimitotic Agents

Antimetabolites

Immunosuppressive Agents

Immunologic Factors

Protective Agents

Milk Thistle

Placebo 420 mg daily in three divided doses for 65 days as control along with \[cisplatin 50-60mg/m2 + fluorouracil 750 mg/m2 +docetaxel 60-80 mg/m2\]

silymarin 420 mg daily in three divided doses for 65 days along with standard chemotherapy \[cisplatin 50-60mg/m2 + fluorouracil 750 mg/m2 +docetaxel 60-80 mg/m2 control

Silymarin 420 mg in 3 divided dose plus standard chemotherapy

placebo tablets: 420 mg in 3 divided dose

Placebo

All patients will receive standard chemotherapy: cisplatin 50-60mg/m2 + fluorouracil 750 mg/m2 + docetaxel 60-80 mg/m2

chemotherapy

Simin Dashti-Khavidaki, Dr

Cisplatin is a potent chemotherapeutic agent that has been widely used to treat many solid tumours. acute renal failure, despite conservative fluid and electrolyte management, frequently reported adverse event and limiting cisplatin use. Silymarin, a flavonolignan complex isolated from Silybum marianum, has a strong antioxidant, hepatoprotective, anticancer and in animal model nephroprotective properties. Neutrophil gelatinase-associated lipocalin (NGAL) protein is a promising biomarker to detect acute kidney injury due to cisplatin. Milk thistle extract inhibitory effects on epidermal growth factor receptor, vascular endothelial growth factor and insulin-like growth factor-I have shown in the previous in-vitro studies.The aim of present study,a randomized double-blind placebo- controlled clinical trial, to investigate the therapeutic effect of silymarin on cisplatin induced nephrotoxicity and it's impact on chemotherapy. Fifty-eight patients with diagnosed upper gastrointestinal tract carcinomas randomized to silymarin (420mg) or placebo plus chemotherapy \[cisplatin 50-60 mg/m2, 5-fluorouracil mg/m2, docetaxel 60-80 mg/m2 every 21 days\] for 63 day after inclusion. serum creatinin, blood urea nitrogen (BUN), serum and urine electrolyte will be measured daily during chemotherapy.

changes in urine NGAL, serum vascular endothelial growth factor (VEGF)and caspase activity assessed up to 64 days.

This study will look for possible protective effects silymarin on kidney injury in patients receiving cisplatin.

Evaluation of Effects of Silymarin on Cisplatin Induced Nephrotoxicity in Upper Gastrointestinal Adenocarcinoma

Phase 2-3 Study of Silymarin on Cisplatin Induced Nephrotoxicity

All subject receive silymarin at dose of 420mg or placebo in three dose for 65 consecutive day, urine NGAL concentration will be measured.

To assess interaction between silymarin and cancer chemotherapy serum vascular endothelial growth factor will be measured.

To assess interaction between silymarin and cancer chemotherapy Tissue activity of caspase 3will be measured.

Tehran University of Medical Sciences

Skin and Connective Tissue Diseases

Behaviors and Mental Disorders

Nervous System Diseases

Heart and Blood Diseases

Symptoms and General Pathology

Substance Related Disorders

Wounds and Injuries

Breast Neoplasms

Cognitive Dysfunction

Peripheral Nervous System Diseases

Cardiotoxicity

Breast Diseases

Skin Diseases

Cognition Disorders

Neurocognitive Disorders

Mental Disorders

Psychotic Disorders

Neuromuscular Diseases

Heart Diseases

Drug-Related Side Effects and Adverse Reactions

Chemically-Induced Disorders

Radiation Injuries

Antirheumatic Agents

Hematinics

Vasodilator Agents

Respiratory System Agents

Paclitaxel

Albumin-Bound Paclitaxel

Cyclophosphamide

Doxorubicin

Liposomal doxorubicin

Liver Extracts

Nitric Oxide

which will receive four cycles of AC regimen (doxorubicin and cyclophosphamide; each cycle was given every 21 day)

followed by 12 cycles of paclitaxel (each cycle was given in a weekly basis) plus placebo tablets once daily.

which will receive the same regimen plus silymarin 140mg once daily.

Silymarin administration prevent the neuro-degeneration through inhibiting the activation of microglia, silymarin attenuates the activation of glial cell activation in cellular models possibly through inhibition of inducible nitric oxide synthase (iNOS) production, also reported to protect both microglia and astroglia from oxidative insults induced by peroxide in ex vivo system .

It also significantly reduces doxorubicin-pro-oxidative activity and decreases histological changes in liver and heart tissue . The hepato-protective and cardio-protective effects of silymarin may be attributed to its antioxidant capacity, its ability to prevent lipid peroxidation and its ability to increase glutathione concentration.

silymarin was reported to improve cognitive impairment in mice.

which will receive four cycles of AC regimen (doxorubicin and cyclophosphamide; each cycle was given every 21 day) followed by 12 cycles of paclitaxel (each cycle was given in a weekly basis) plus placebo tablets once daily.

Aim of the work This study aims to evaluate the possible beneficial role of silymarin in attenuating both doxorubicin related cardiac and hepatic toxicities and paclitaxel associated peripheral neuropathy and improving cognitive impairment in patients with breast cancer.

This study will be a randomized placebo controlled parallel study. The study will be performed in accordance with the ethical standards of Helsinki declaration in 1964 and its later amendments.

Group one: (Placebo group; n=28) which will receive four cycles of AC regimen (doxorubicin and cyclophosphamide; each cycle was given every 21 day) followed by 12 cycles of paclitaxel (each cycle was given in a weekly basis) plus placebo tablets once daily.

Group two: (Silymarin group; n=28) which will receive the same regimen plus silymarin 140mg once daily

Breast cancer represents the most frequently diagnosed malignancy and the second most common cause of cancer death worldwide. In Egypt, breast cancer is the most common malignancy in women, accounting for 38.8% of cancers in this population, with the estimated number of breast cancer cases nearly 22,700 in 2020 and forecasted to be approximately 46,000 in 2050 .

Paclitaxel and doxorubicin are cytotoxic agents that are commonly used for treatment of breast cancer. Despite their effectiveness, both paclitaxel and doxorubicin are associated with cumulative and potential neurotoxicity and cardiotoxicity respectively . Paclitaxel induced peripheral neuropathy (PN) is a consequence of activation of the inflammatory cascade with subsequent increased pro-inflammatory cytokines production including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) . Moreover, paclitaxel can up-regulate matrix metalloproteinase-3 (MMP3) which plays an important role in the inflammatory and degenerative processes following nerve injury .

Oxidative stress plays a critical role in doxorubicin associated cardiotoxicity through direct cellular damage, induction of apoptosis and activation of nuclear factor- Kabba B (NF-ĸB) which in turn stimulates the production and release of inflammatory mediators .

Hepatotoxicity from doxorubicin was reported and it is likely due to direct toxic injury to the liver. Doxorubicin and its analogues are metabolized in the liver via microsomal enzymes, and production of a toxic or immunogenic intermediate may trigger liver injury with subsequent elevation of Serum aminotransferase.In addition, it was reported that, doxorubicin related hepatotoxicity is a consequence of free radical formation and oxidative stress and antioxidants may protect against doxorubicin-induced toxicity in the liver .

Although, the underlying neuro-protective mechanism of silymarin is mainly due to its capacity to inhibit oxidative stress in the brain, it also confers additional neuro-protection by influencing other pathways such as inflammatory pathways . Silymarin has been implicated in protecting neurons against oxidative stress and nitrosative stress . Silymarin was reported to exert direct effect on neuronal oxidant status .

Silymarin administration in a lipopolysaccharide induced animal model of peripheral neuropathy prevented the dopaminergic neuro-degeneration through inhibiting the activation of microglia. Other in-vitro studies revealed that, silymarin attenuates the activation of glial cell activation in cellular models possibly through inhibition of inducible nitric oxide synthase (iNOS) production . Silymarin was also reported to protect both microglia and astroglia from oxidative insults induced by peroxide in ex vivo system .

Treatment with silymarin prevents the increase in AST and creatine kinase (CK) serum activity and myocardial excitability in rats caused by doxorubicin . It also significantly reduces doxorubicin-pro-oxidative activity and decreases histological changes in liver and heart tissue . The hepato-protective and cardio-protective effects of silymarin may be attributed to its antioxidant capacity, its ability to prevent lipid peroxidation and its ability to increase glutathione concentration .

Cognitive impairment in patients with breast cancer began to appear in the literature in the 1990s, coincident with the increasing use of postoperative adjuvant chemotherapy . In two recent preclinical studies, silymarin was reported to improve cognitive impairment in mice, and these former studies suggested that silymarin may be a therapeutic agent for cognitive decline .

This study will be a randomized placebo controlled parallel study. The study will be performed in accordance with the ethical standards of Helsinki declaration in 1964 and its later amendments.

Group one: (Placebo group; n=28) which will receive four cycles of AC regimen (doxorubicin and cyclophosphamide; each cycle was given every 21 day) followed by 12 cycles of paclitaxel (each cycle was given in a weekly basis) plus placebo tablets once daily.

Group two: (Silymarin group; n=28) which will receive the same regimen plus silymarin 140mg once daily.

* Blood sample collection and biochemical assessment:

  1. N-terminal prohormone of brain naturetic peptide (NT-proBNP" ) and liver panel.
  2. myeloperoxidase (MPO)
  3. neurofilament light chain (NFL)
  4. andnuclear factor- Kabba B p65 (NF-ĸB p65) or TNF-alpha
* Clinical assessment of chemotherapy induced toxicities:
* Doxorubicin related cardiotoxicity will be assessed through - Echocardiography at baseline and after the last doxorubicin/ cyclophosphamide (AC) cycle.
* Paclitaxel induced peripheral sensory neuropathy will be done through: - The implication of National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE, Version 5, 2017) for grading of neuropathy at baseline and by the end of every two paclitaxel cycles.
* The use of Neurotoxicity- 12 item questionnaire score (Ntx-12) from the validated Functional Assessment of Cancer Therapy/Gynecologic Oncology Group "FACT/GOG-Ntx-12" at baseline and by the end of every two paclitaxel cycles.
* The assessment of the severity of neuropathic pain through brief pain inventory short form "BPI-SF" worst item. Severity of neuropathic pain will be assessed at baseline and by the end of every two paclitaxel cycles.
* Cognitive impairment will be assessed using the brief assessment of impaired Cogentin questionnaire (BASIC-Q).
* Primary and secondary outcomes:

The primary outcome is the change in ejection fraction and percentage of patients with peripheral sensory neuropathy grade ≥ 2 with the variation of both 12-item neurotoxicity questionnaire (Ntx-12) total score and pain rating scale score. The secondary outcome is the changes in serum levels of the measured biological markers.

- Sample size calculation: According to the results of a previous study, the total number of subjects required to detect the cardio-protective effect of silymarin in patients with different types of cancer receiving anthracyclines containing chemotherapy was 25 patients . With 5% significance level, 80% statistical power and an attrition rate of 10%, the initial sample size required for the current study is 28 patients in each group.

-Ethical approval: The study will be approved by the Research Ethics Committee of Tanta University. The study will be registered as a clinical trial at ClinicalTrials.gov. All participants will be informed about the benefits and risks of the study. Any unexpected risks that will appear during the course of the research will be clarified to the participants and to the ethical committee on time. The data of the enrolled patients will be confidential. All enrolled patients will give their written informed consents. The study will be conducted between October 2022 and October 2024.

Role of Silymarin in Chemotherapy Toxicity and Cognition Improvement in Breast Cancer Patients

The Possible Protective Role of Silymarin Against Chemotherapy Induced Toxicities and Cognitive Impairment in Breast Cancer Patients

Doxorubicin related cardiotoxicity will be assessed through :Echocardiography at baseline, Before starting the first chemotherapy cycle (baseline), after the last AC cycle (for assessment of N-terminal prohormone of brain naturetic peptide "NT-proBNP" ) and after the last doxorubicin/ cyclophosphamide (AC) cycle.

change in percentage of patients with peripheral sensory neuropathy grade ≥ 2 with the variation of both 12-item neurotoxicity questionnaire (Ntx-12) total score and pain rating scale score.

N-terminal prohormone of brain naturetic peptide "NT-proBNP" ) liver panel myeloperoxidase (MPO) neurofilament light chain (NFL) nuclear factor- Kabba B p65 (NF-ĸB p65) or TNF-alpha

Tanta University

principal investigator

Digestive System Diseases

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Micronutrients

Irinotecan

Capecitabine

Bevacizumab

Leucovorin

Group I (Control group ; n=32) which will receive FOLFIRI regimen (5-flourouracil, leucovorin, irinotecan) or XELIRI (Capecitabine and irinotecan) with or without target therapy (Bevacizumab).

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.

participants in silymarin group will receive silymarin 140 mg once daily.

Shimaa Yassin, pharmacist

faculty of Pharmacy

shimaa yassin, pharmacist

Tarek Mostafa, professor

Sahar Elhaggar, professor

Mohammed Alam El-Din, professor

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).

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.

Effect of Silymarin in Metastatic Colorectal Cancer Patients

The Possible Anticancer Effect of Silymarin in Patients With Metastatic Colorectal Cancer Receiving Chemotherapy.

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.

As Tumor Marker if the baseline is elevated.

principal Investigator

Blood and Lymph Conditions

Immune System Diseases

Rare Diseases

Leukemia

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Lymphoma

Neoplasms by Histologic Type

Hematologic Diseases

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Acute Graft Versus Host Disease

Childhood Acute Lymphoblastic Leukemia

Lymphosarcoma

silymarin

Kara Kelly, MD

RATIONALE: Silymarin (milk thistle extract) is an herb that may be effective in treating liver disorders caused by cancer therapy.

PURPOSE: Randomized phase II trial to study the effectiveness of silymarin in treating patients who have acute lymphoblastic leukemia with chemotherapy-related side effects to the liver.

OBJECTIVES:

* Determine the effect of silymarin, in terms of liver function tests, in patients with acute lymphoblastic leukemia receiving hepatotoxic chemotherapy.
* Determine the effect of this drug on free and conjugated serum silibinin values in these patients.
* Determine the serum antioxidant capacity by Oxygen Radical Absorbance Capacity in patients treated with this drug.
* Determine the oxidative damage, as determined by 8-oxodeoxyguanosine adducts, in patients treated with this drug.

OUTLINE: This is a randomized, double-blind, placebo-controlled study. Patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients receive oral silymarin daily for 28 days.
* Arm II: Patients receive oral placebo as in arm I. Patients are followed at day 56.

PROJECTED ACCRUAL: A total of 50 patients (25 per treatment arm) will be accrued for this study.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Evaluation of Effects of Silymarin on Cisplatin Induced Nephrotoxicity in Upper Gastrointestinal Adenocarcinoma	NCT01829178	Upper GI Cancer Cisplatin Adver...	Silymarin Placebo chemotherapy	18 Years - 70 Years	Tehran University of Medical Sciences
Role of Silymarin in Chemotherapy Toxicity and Cognition Improvement in Breast Cancer Patients	NCT05595109	Breast Cancer Peripheral Neur... Cardiac Toxicit... Hepatic Toxicit... Cognitive Impai...	Silymarin Placebo	18 Years -	Tanta University
Effect of Silymarin in Metastatic Colorectal Cancer Patients	NCT05631041	Metastatic Colo...	Silymarin	18 Years -	Tanta University
Silymarin (Milk Thistle Extract) in Treating Patients With Acute Lymphoblastic Leukemia Who Are Receiving Chemotherapy	NCT00055718	Drug/Agent Toxi... Leukemia	silymarin	2 Years - 21 Years	National Cancer Institute (NCI)

Spots Global Cancer Trial Database for silymarin

Every month we try and update this database with for silymarin cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for silymarin

Every month we try and update this database with for silymarin cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for silymarin cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.