A randomized, controlled, double-blind, pilot study of milk thistle for the treatment of hepatotoxicity in childhood acute lymphoblastic leukemia (ALL).
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.
Ladas
Elena J
EJ
Division of Pediatric Oncology, Columbia University Medical Center, New York, New York 10032, USA.
Kroll
David J
DJ
Oberlies
Nicholas H
NH
Cheng
Bin
B
Ndao
Deborah H
DH
Rheingold
Susan R
SR
Kelly
Kara M
KM
D000293:Adolescent; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D056486:Chemical and Drug Induced Liver Injury / Q000628:therapy*; D002648:Child; D002675:Child, Preschool; D004311:Double-Blind Method; D004353:Drug Evaluation, Preclinical; D004347:Drug Interactions; D005260:Female; D006801:Humans; D007223:Infant; D008111:Liver Function Tests; D008297:Male; D020944:Silybum marianum / Q000009:adverse effects; D008517:Phytotherapy; D010865:Pilot Projects; D010919:Placebos; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000150:complications / Q000188:drug therapy*
D000970:Antineoplastic Agents; D010919:Placebos