Cancer Chemotherapy and Pharmacology

, Volume 57, Issue 3, pp 309–316

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

  • Peter J. Tobin
  • Philip Beale
  • Leesa Noney
  • Sandy Liddell
  • Laurent P. Rivory
  • Stephen Clarke
Original Article

DOI: 10.1007/s00280-005-0053-0

Cite this article as:
Tobin, P.J., Beale, P., Noney, L. et al. Cancer Chemother Pharmacol (2006) 57: 309. doi:10.1007/s00280-005-0053-0

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/m2 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.

Keywords

Chrysin CPT-11 Diarrhoea Glucuronidation Irinotecan UGT1A1 SN-38 

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Peter J. Tobin
    • 1
  • Philip Beale
    • 2
  • Leesa Noney
    • 2
  • Sandy Liddell
    • 2
  • Laurent P. Rivory
    • 2
  • Stephen Clarke
    • 2
    • 3
  1. 1.Department of PharmacologyUniversity of SydneySydneyAustralia
  2. 2.Sydney Cancer CentreRoyal Prince Alfred HospitalSydneyAustralia
  3. 3.Department of OncologyConcord HospitalConcordAustralia

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