LIME

Full title: Observational study of frequency and causes of impaired liver metabolism of cyclophosphamide in breast cancer
Cancer type: Breast
Status: Closed
Brief description:

 

Evidence suggests that cancer may affect the activity of a liver enzyme (CYP2C19) that helps to activate the anticancer drug cyclophosphamide, an important agent in the treatment of breast cancer.

There are large differences in the way each person responds to anticancer drugs. Some of these differences relate to the way the body processes drugs using enzymes found in the liver. One reason for different reactions to cancer treatment may be differences in amounts of these liver enzymes or differences in the way they work. The liver enzyme that we are studying is called CYP2C19. Most of the activity of CYP2C19 is inherited. CYP2C19 can activate cyclophosphamide, a drug used in your treatment. Our recent work suggested that in the activity of this CYP2C19 gene is regulated differently in cancer patients than in healthy people, so that some cancer patients may have extremely low drug processing activity. It is possible to measure CYP2C19 activity by giving them a small dose of a drug called proguanil. This medication is often taken by travellers for prevention of malaria and is processed by the body in a similar way to cyclophosphamide.

In this study we would like to measure the activity of this CYP2C19 enzyme by measuring proguanil blood concentrations after a test dose and also directly measure the activation of cyclophosphamide in blood samples.

By learning more about the things that influence a person’s ability to process drugs, we might be better able in the future to fine-tune the dose of cancer drugs to the individual.

Sites: Auckland
Lead Investigator: Associate Professor Nuala Helsby
Contact: Sarah Benge (s.benge@auckland.ac.nz)
Sponsor: University of Auckland
Funder: Cancer Society
Trial Registry reference: ACTRN12612001170819 (click for more details)
Ethics number: NTX/12/06/052
Publications: Helsby, NA, Yang, J, Goldthorpe, M, Barrett, C, Wilson, G, Broome, R, Findlay, M, Porter, D CYP2C19 phenoconversion in patients with breast cancer and alterations in bioactivation of cyclophosphamide. Proceedings of 12th Congress of European Association of Clinical Pharmacology,.Madrid, Spain. Clin Therapeutics 2015 37: 8 Suppl e41