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Cancer Chemother Pharmacol. 2006 Feb;57(3):309-16. Epub 2005 Jul 8.

A pilot study on the safety of combining chrysin, a non-absorbable inducer of UGT1A1, and irinotecan (CPT-11) to treat metastatic colorectal cancer.

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  • 1Department of Pharmacology, University of Sydney, NSW, Australia.

Abstract

PURPOSE:

Recently, it was shown that chrysin causes upregulation of UGT1A1 in Caco-2 intestinal cells. Therefore, we proposed that oral chrysin may reduce irinotecan (CPT-11) induced diarrhoea by shifting the SN-38G/SN-38 equilibrium towards the inactive SN-38G in the gastrointestinal mucosa. The purpose of this study was to examine the safety of combining single agent CPT-11 with chrysin.

PATIENTS AND METHODS:

Twenty patients with previously treated advanced colorectal cancer were administered chrysin twice daily for 1 week preceding and succeeding treatment with single agent CPT-11 (350 mg/m(2) over 90 min every 3 weeks). Loperamide usage and bowel frequency/consistency were recorded by patients into a study diary and blood samples were collected for CPT-11 pharmacokinetic analysis.

RESULTS:

There were no observable toxicities that could be attributed to chrysin use. The grades and frequency of delayed diarrhoea were mild, with only 10% of patients experiencing grade 3 toxicity. Loperamide usage was also modest with a median of 1-5 tablets per cycle (range: 0-22). Pharmacokinetic results revealed a mass ratio of plasma SN-38G/SN-38, which was very similar to historical controls (7.15 +/- 5.67, n = 18).

CONCLUSIONS:

These findings, combined with the observation of clinical activity and grade 3/4 neutropenia in 25% of patients, suggest that combining chrysin with CPT-11 may be a safe and potentially useful means of preventing diarrhoea, although this needs to be further investigated in the setting of a randomised trial.

PMID:
16003560
[PubMed - indexed for MEDLINE]
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