A pilot study on the safety of combining chrysin, a non-absorbable inducer of UGT1A1, and irinotecan (CPT-11) to treat metastatic colorectal cancer. Cancer chemotherapy and pharmacology. [Cancer Chemother Pharmacol] Journal article | | Title | A pilot study on the safety of combining chrysin, a non-absorbable inducer of UGT1A1, and irinotecan (CPT-11) to treat metastatic colorectal cancer. | | Author(s) | Tobin PJ, Beale P, Noney L, Liddell S, Rivory LP, Clarke S | | Institution | Department of Pharmacology, University of Sydney, NSW, Australia. | | Source | Cancer Chemother Pharmacol 2006 Feb; 57(3):309-16. | | MeSH | Administration, Oral
Antineoplastic Combined Chemotherapy Protocols
Area Under Curve
Caco-2 Cells
Camptothecin
Chromatography, High Pressure Liquid
Colorectal Neoplasms
Comparative Study
Diarrhea
Drug Administration Schedule
Enzyme Induction
Female
Flavonoids
Glucuronates
Glucuronosyltransferase
Humans
Injections, Intravenous
Male
Middle Aged
Neoplasm Metastasis
Neutropenia
Pilot Projects
| | 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. | | Language | eng | | Pub Type(s) | Clinical Trial
Journal Article
| | PubMed ID | 16003560 |
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