After 56 days of oral treatment with milk thistle in capsule form, children in a placebo-controlled trial showed significantly lower levels of aspartate aminotransferase (AST) and trends toward lower alanine aminotransferase (ALT) and bilirubin, according to Kara M. Kelly, MD, of Columbia University, and colleagues.
The study "provides preliminary evidence that milk thistle may be a safe, effective, supportive-care agent," the researchers concluded in an online report in Cancer.
"Milk thistle needs to be studied further, to see how effective it is for a longer course of treatment, and whether it works well in reducing liver inflammation in other types of cancers and with other types of chemotherapy," Kelly said in a press release issued by the American Cancer Society, publisher of Cancer. "However, our results are promising as there are no substitute medications for treating liver toxicity."
Milk thistle (Silybum marianum) is an herbal plant, native to Mediterranean Europe, North Africa and the Middle East, that has been shown to protect the liver and kidneys against damage from known toxins. Extracts are widely available in drugstores and herbal medicine shops, as well as from Internet vendors.
The version used in the current study was a 1:2 mixture of silibinin, believed to be the most active component of the herb, and soy phosphatidylcholine to improve the former's bioavailability.
Among the herb's purported benefits is limiting liver toxicity from cancer chemotherapy, but this had not previously been tested in a placebo-controlled trial.
So Kelly and colleagues assigned 50 children receiving treatment for ALL with a regimen of vincristine, methotrexate, 6-mercaptopurine or thioguanine, and prednisone or dexamethasone to receive daily doses of the milk thistle product or placebo.
Participants ranged in age from under two to 19 (mean age 8.7 in the milk thistle group, 7 in the placebo group). About 60% in each group were classed as standard risk and the rest were high risk.
Milk thistle was given in quantities designed to equate to a silibinin dose of 5.1 mg/kg/day, for 28 days.
Levels of AST, ALT, and bilirubin were measured at baseline and at days 28 and 56.
The only significant difference between the milk thistle and placebo groups in these outcomes was for AST at day 56, with mean levels of about 47 U/L with milk thistle versus 67 U/L with placebo (P=0.04). Mean AST levels were also lower at day 28, but the difference was smaller and not significant.
ALT levels were slightly higher on day 28 in the milk thistle group versus placebo. On day 56, mean ALT levels were 122 U/L with milk thistle versus 140 U/L with placebo, but the P value remained above 0.05.
Bilirubin levels were virtually identical in the two groups at day 28. They were somewhat lower at day 56 with milk thistle (0.70 versus 0.87 in the placebo group) but this also failed to reach significance.
Chemotherapy dose reductions because of toxicity were also somewhat less common in the milk thistle group, with 61% taking reductions compared with 73% of the placebo group (not significant).
Milk thistle appeared to have no impact on delays in planned chemotherapy, and grade 3-4 toxicities were, if anything, more frequent in the actively-treated group.
During the first four weeks of treatment, five patients in the milk thistle group and three taking placebo experienced grade 3-4 hepatic toxicity. From day 28 to 56, eight children on milk thistle and five in the placebo group had grade 3-4 hepatic toxicity.
Kelly and colleagues said there were no toxicities or other untoward results attributable to the milk thistle. They suggested that the equivocal efficacy findings could have resulted from inadequate dosing of milk thistle, especially since testing of plasma samples from 18 children in the study failed to find detectable levels of silibinin in any patient.
"An evaluation of clinical literature shows a wide range of therapeutic doses and duration," they noted in their report, adding that they had chosen a "conservative" dose level and duration to be on the safe side.
It's also possible that children metabolize silibinin at different rates from adults, which would account for the lack of detectable silibinin in plasma samples.
Finally, Kelly and colleagues noted that compliance was poorer in the milk thistle group: 68% of planned doses were given, compared with 96% of placebo capsules. The milk thistle product was identical in smell and taste to the placebo.
The only difference the researchers identified that might have accounted for the compliance disparity was age. The milk thistle group had a significantly higher mean age, and noncompliant patients were significantly older than compliant children (mean 13.1 versus 6.9 years old, P=0.01).
"Future clinical trials should explore milk thistle in the setting of patients in which hepatic toxicity prevents provision of the recommended chemotherapy in individuals with cancer," Kelly and colleagues concluded.
The study was funded by the American Institute for Cancer Research, the Tamarind Foundation, and the National Cancer Institute. Study drugs were donated by Thorn Research, which produces the milk thistle extract used in the study.
Study authors reported no potential conflicts of interest.
Source Reference:
Ladas E, 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.
Reader Comments
to our Newsletter