Hormone sensitive breast cancer
Conditions
Interventions
Eleven patients on steady-state tamoxifen treatment will start with tamoxifen
alone for 7 days, followed by tamoxifen with probenecid for 14 consecutive
days. Patients will be admitted to the hospit
Sponsors
Erasmus MC, Universitair Medisch Centrum Rotterdam
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Age * 18 years 2. Patients with a confirmed diagnosis of primary or advanced breast cancer, who are on tamoxifen treatment for at least three months (steady state concentration). 3. A CYP2D6 poor metabolizer or intermediate metabolizer phenotype 4. WHO performance * 1 (Appendix B) 5. Able and willing to sign the informed consent form prior to screening evaluations 6. Willing to abstain from strong CYP3A4, CYP2D6, CYP2C9/2C19, UGT and P-gp inhibitors or inducers, herbal or dietary supplements or other over-the-counter medication besides paracetamol. 7. Adequate kidney function defined as: GFR > 50 ml/min/1.73 m2
Exclusion criteria
Exclusion criteria: 1. Pregnant or lactating patients 2. Patients with known impaired drug absorption (e.g. gastrectomy and achlorhydria) 3. Use of drugs which may show an increased systemic exposure when taken concomitantly with probenecid e.g. methotrexate, penicillin, cephalosporin or chinolon antibiotics or NSAIDs. 4. Patients with known blood dyscrasias, porphyria, uric acid kidney stones or until an acute gouty attack has subsided. 5. Known serious illness or medical unstable conditions that could interfere with this study requiring treatment (e.g. HIV, hepatitis, Varicella zoster or herpes zoster, organ transplants, kidney failure (GFR
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary endpoint of this study is the Area under the curve (AUC) of endoxifen. The AUC of endoxifen during tamoxifen monotherapy will be compared to the AUC of endoxifen during concomitant treatment of tamoxifen with probenecid. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary endpoints include the difference in AUC for tamoxifen and endoxifen-glucuronide and other pharmacokinetic parameters of endoxifen, tamoxifen and endoxifen-glucuronide (i.e. clearance, maximum concentration (Cmax), minimal concentration (Ctrough) and time until maximum concentration (tmax) and elimination half-life (t*)). Furthermore, an explorative analysis on difference in side-effects per treatment phase will be performed. | — |
Countries
Netherlands
Outcome results
None listed