None listed
Conditions
Brief summary
Evidence suggests that 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.
Interventions
Participant patients will be dispensed with a 200 mg dose of the probe drug, proguanil on two separate occasions. The patients will be requested to take two tablets containing 100 mg each, by mouth three hours before the commencement of chemotherapy. The patients will also be requested to take two tablets containing 100 mg each, by mouth three hours prior to the commencement of the 3rd cycle of chemotherapy.
The duration between the 1st and 3rd cycles of chemotherapy will be dependent on the pat
Participant patients will be dispensed with a 200 mg dose of the probe drug, proguanil on two separate occasions. The patients will be requested to take two tablets containing 100 mg each, by mouth three hours before the commencement of chemotherapy. The patients will also be requested to take two tablets containing 100 mg each, by mouth three hours prior to the commencement of the 3rd cycle of chemotherapy. The duration between the 1st and 3rd cycles of chemotherapy will be dependent on the patients own chemotherapy schedules.
Sponsors
University of Auckland
Eligibility
Sex/Gender
All
Age
19 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Age>18 ECOG (Eastern Cooperative Oncology Group) Performance Status 0-2 Histologically confirmed breast cancer To receive intravenous cyclophosphamide as part of adjuvant, neoadjuvant or first line chemotherapy for breast cancer as part of standard care. Staging investigations in process (should not be greater than 2 weeks after start of chemotherapy). Patients must be able to provide written informed consent Aspartate transaminase (AST), Alaninine transaminase (ALT) =< 2.5 X upper limit of normal (ULN) for institution Alkaline phosphatase <5x ULN Bilirubin =< ULN, except when due to Gilbert’s Disease Creatinine <1.5 ULN
Exclusion criteria
Patients receiving medication which is either a CYP2C19 inhibitor or inducer, and where a washout period of 5 days is not clinically feasible Chronic inflammatory condition such as systemic lupus erythematosis, inflammatory bowel disease, other autoimmune phenomenon or active chronic infection Active infections (e.g. wound) at time of chemotherapy Pregnant or breast feeding Other active malignancy within the last 5 years, excluding non-melanoma skin cancers, or preinvasive cervical cancer that has been treated definitively
Outcome results
None listed