Milk Thistle Cuts Liver Toxicity from ALL Chemotherapy

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Milk Thistle Cuts Liver Toxicity from ALL Chemotherapy

Ladas EJ, Kroll DJ, Oberlies NH, et al. A randomized, controlled, double-blind, pilot study of milk thistle for the treatment of hepatotoxicity in childhood acute lymphoblastic leukemia (ALL). Cancer 2009; DOI: 10.1002/cncr.2472.

doi 10.1002/cncr.24723



Original Article
A randomized, controlled, double-blind, pilot study of milk thistle for the treatment of hepatotoxicity in childhood acute lymphoblastic leukemia (ALL)

Elena J. Ladas, MS, RD 1, David J. Kroll, PhD 2, Nicholas H. Oberlies, PhD 3, Bin Cheng, PhD 4, Deborah H. Ndao, MPH 1, Susan R. Rheingold, MD 5, Kara M. Kelly, MD 1 *
1Division of Pediatric Oncology, Columbia University Medical Center, New York, New York
2Department of Pharmaceutical Sciences, North Carolina Central University, Biomanufacturing Research Institute and Technology Enterprise, Durham, North Carolina
3Natural Products Laboratory, Research Triangle Institute, Research Triangle Park, North Carolina
4Department of Biostatistics, Columbia University Medical Center, Mailman School of Public Health, New York, New York
5Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
email: Kara M. Kelly (
*Correspondence to Kara M. Kelly, Columbia University Medical Center, Pediatric Oncology, 161 Ft. Washington, 7th floor, New York, NY 10032
Informed consent was obtained for each patient recruited to the clinical trial.
Fax: (212) 305-5848

acute lymphoblastic leukemia • hepatotoxicity • milk thistle • complementary medicine • childhood cancer


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.

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.

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.

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 Society

Received: 5 March 2009; Revised: 20 April 2009; Accepted: 22 April 2009