A randomized, controlled, double‐blind, pilot study of milk thistle for the treatment of hepatotoxicity in childhood acute lymphoblastic leukemia (ALL)
Open Access
- 14 December 2009
- Vol. 116 (2), 506-513
- https://doi.org/10.1002/cncr.24723
Abstract
BACKGROUND: Despite limited preclinical and clinical investigations, milk thistle (MT) is often used for the treatment of chemotherapy‐associated hepatotoxicity. Limited treatment options exist for chemotherapy‐related hepatoxicity. Given the wide use of MT, the authors investigated MT in both the laboratory and a clinical setting. METHODS: In a double‐blind study, children with acute lymphoblastic leukemia (ALL) and hepatic toxicity were randomized to MT or placebo orally for 28 days. Liver function tests were evaluated during the study period. To assess MT in vitro, the authors evaluated supratherapeutic concentrations in an ALL cell line. RESULTS: Fifty children were enrolled. No significant differences in frequency of side effects, incidence and severity of toxicities, or infections were observed between groups. There were no significant changes in mean amino alanine transferase (ALT), aspartate amino transferase (AST), or total bilirubin (TB) at Day 28. At Day 56, the MT group had a significantly lower AST (P = .05) and a trend toward a significantly lower ALT (P = .07). Although not significantly different, chemotherapy doses were reduced in 61% of the MT group compared with 72% of the placebo group. In vitro experiments revealed no antagonistic interactions between MT and vincristine or L‐asparaginase in CCRF‐CEM cells. A modest synergistic effect with vincristine was observed. CONCLUSIONS: In children with ALL and liver toxicity, MT was associated with a trend toward significant reductions in liver toxicity. MT did not antagonize the effects of chemotherapy agents used for the treatment of ALL. Future study is needed to determine the most effective dose and duration of MT and its effect on hepatotoxicity and leukemia‐free survival. Cancer 2010. © 2009 American Cancer SocietyKeywords
This publication has 21 references indexed in Scilit:
- Early postinduction intensification therapy improves survival for children and adolescents with high-risk acute lymphoblastic leukemia: a report from the Children's Oncology GroupBlood, 2008
- Outcome After Relapse Among Children With Standard-Risk Acute Lymphoblastic Leukemia: Children's Oncology Group Study CCG-1952Journal of Clinical Oncology, 2007
- Milk thistle for alcoholic and/or hepatitis B or C virus liver diseasesEmergencias, 2007
- Clinical Applications of Silybum marianum in OncologyIntegrative Cancer Therapies, 2007
- Intrathecal triple therapy decreases central nervous system relapse but fails to improve event-free survival when compared with intrathecal methotrexate: results of the Children's Cancer Group (CCG) 1952 study for standard-risk acute lymphoblastic leukemia, reported by the Children's Oncology GroupBlood, 2006
- In Defense of NCCAMScience, 2006
- Pilot Study of Oral Silibinin, a Putative Chemopreventive Agent, in Colorectal Cancer Patients: Silibinin Levels in Plasma, Colorectum, and Liver and Their Pharmacodynamic ConsequencesClinical Cancer Research, 2006
- Asparaginase Antibody and Asparaginase Activity in Children With Higher-Risk Acute Lymphoblastic LeukemiaJournal of Pediatric Hematology/Oncology, 2004
- Prognostic Significance of Methotrexate and 6-Mercaptopurine Dosage During Maintenance Chemotherapy for Childhood Acute Lymphoblastic LeukemiaPediatric Hematology and Oncology, 1991
- Pharmacokinetic studies on IdB 1016, a silybin-phosphatidylcholine complex, in healthy human subjectsEuropean Journal of Drug Metabolism and Pharmacokinetics, 1990