women with early stage breast cancer using adjuvant tamoxifen Dutch: patientes met vroeg-stadium mammacarcinoom behandeld met adjuvant tamoxifen
Conditions
Interventions
None:
Tamoxifen is only temporarily (2 months) escalated in a selected group of 12 poor and 12 intermediate metabolizers for pharmacokinetic purposes without expected effect on clinical outcome in t
Sponsors
Leiden University Medical Center (LUMC)
Leiden, the Netherlands
Eligibility
Inclusion criteria
Inclusion criteria: 1. Pre- and postmenopausal women who will receive tamoxifen or have already been using tamoxifen during a maximum period of one year, as part of a standard adjuvant therapy for newly diagnosed breast cancer. 2. Willing and able to give written informed consent (separate for documentation and pharmacokinetics study). 3. Age >= 18 years.
Exclusion criteria
Exclusion criteria: 1. Other malignancy within the previous 5 years (except adequately treated in situ carcinoma of cervix or basal cell carcinoma). 2. Hormone receptor negative primary tumors. Exclusion criteria for PHARMACOKINETICS study only: 1. A medical history of venous thromboembolic events (deep venous thrombosis or pulmonary embolism). 2. Patients who are pregnant or breastfeeding. 3. Patients with a prolonged QT interval on ECG registration. 4. Hemoglobin 2.5 times the upper limit of normal.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. To associate CYP2D6 genotype and tamoxifen metabolite plasma concentration to relapse free survival (RFS), disease free survival (DFS) and overall survival (OS) (documentation study). 2. To investigate the effect of a temporary one-step dose escalation of tamoxifen on endoxifen plasma concentration in poor and intermediate metabolizers (pharmacokinetics study). Amendment: To correlate the CYP2D6 genotype and the serum endoxifen concentrations to the CYP2D6 phenotype determined by a dextromethorphan breath test (DM-BT). | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. To evaluate tamoxifen toxicity in patients participating in dose escalation Third Amendment: Statistical Analysis Plan for the documentation study. Secondary objectives: 1. To associate endoxifen concentrations to disease-free survival (DFSt), overall survival (OS), relapse-free survival complete (RFSc) and disease-free survival (DFSc). 2. To associate CYP2D6 predicted phenotype to DFSt, OS, RFSc and DFSc. • DFSt was defined as the time from study enrolment until loco- regional or distant recurrence or second breast cancer or death without recurrence. In case of a subsequent switch to an aromatase inhibitor, patients were censored at the time of tamoxifen discontinuation. • OS was defined as the time from study enrolment until death by any cause. • RFSc was defined as the time from study enrolment until loco- regional or distant recurrence or second breast cancer. In case of a subsequent switch to an aromatase inhibitor, patients were not censored at the time of tamoxifen discontinuation, but the complete period until an event or lost to follow-up was used. • DFSc was defined as the time from study enrolment until loco- regional or distant recurrence or second breast cancer or death without recurrence. In case of a subsequent switch to an aromatase inhibitor, patients were not censored at the time of tamoxifen discontinuation, but the complete period until an event or lost to follow-up were used. | — |
Contacts
Public ContactV.O. Dezentje
Leiden University Medical Center (LUMC) Department of Clinical Oncology and Clinical Pharmacy and Toxicology PO Box 9600
Outcome results
None listed