Full title: The effect of cancer progression on the activity of the liver enzyme called CYP2C19 in patients with carcinoma of the gastrointestinal tract using the probe drug proguanil.
Cancer type: Gastrointestinal
Status: Closed
Brief description:


This study builds on our previous work looking at how the body “processes” cancer drugs. Many drugs are metabolised in the liver by enzymes of the cytochrome P450 family. The level of enzyme activity varies from person to person. This is important, as poor metabolism of some drugs may put some people at greater risk of side effects, while extensive metabolism may mean the drug does not work as well. Cyclophosphamide is an important anticancer drug that is metabolised by a liver enzyme called CYP2C19. About 3% of Caucasian populations are genetically poor metabolisers for CYP2C19. Our recent work suggested that people may actually lose CYP2C19 metabolism simply through the fact of having cancer. It is possible to measure CYP2C19 activity in an individual by giving them a small dose of a test drug such as proguanil. In this study we plan to see how CYP2C19 metabolism changes (i) between people with different amounts of cancer in their body and (ii) in individual people with cancer as time goes on and their cancer changes. The knowledge gained from this study will help us in future as we try to better tailor cancer drug doses to the individual.
Sites: Auckland
Lead Investigator: Associate Professor Nuala Helsby
Contact: Sarah Benge (s.benge@auckland.ac.nz)
Sponsor: Not applicable
Funder: Genesis Oncology Trust
Trial Registry reference: ACTRN12609000056291 (click for more details)
Ethics number: NTX/08/07/060
Publications: BURNS K, GOLDTHORPE M, PORTEOUS F, BROWETT P, HELSBY NA. CYP2C19 genotype-phenotype discordance in patients with multiple myeloma leads to an acquired loss of drug metabolising activity. Cancer Chemotherapy and Pharmacology 73: (3) 651-655

KATHRYN E. BURNS, WING-YEE LO, MICHAEL P. FINDLAY, GEORGE LAKING, NUALA A. HELSBY. Genotype-phenotype discordance of the hepatic drug metabolism enzyme CYP2C19 in gastrointestinal cancer patients In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; 2014. Abstract nr {5548}. Cancer Res October 1, 2014 74; 5548

Burns KE, Lo W-Y, Findlay MP, Sharples K, Laking G, Helsby NA High CYP2C19 phenotypic variability in gastrointestinal cancer patients Cancer Chemotherapy Pharmacology (2016) 77:195–204