A randomized, controlled, double-blind, pilot study of milk thistle for the
treatment of hepatotoxicity in childhood acute lymphoblastic leukemia (ALL).
Author(s): Ladas EJ, Kroll DJ, Oberlies NH, Cheng B, Ndao DH, Rheingold SR, Kelly KM.
Affiliation(s): Division of Pediatric Oncology, Columbia University Medical Center, New York, New
York 10032, USA.
Publication date & source: 2010, Cancer. , 116(2):506-13
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.
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