Breast Cancer
Conditions
Interventions
1. Patients will be switched from paroxetine (potent CYP2D6 inhibitor) to treatment with a weak CYP2D6 inhibiting antidepressant (venlafaxine or escitalopram)
2. Pharmacokinetic sampling.
Sponsors
Erasmus Medical Center - Daniel den Hoed Cancer Center, Dept of Medical Oncology
Eligibility
Inclusion criteria
Inclusion criteria: 1. Histological or cytological confirmed diagnosis of breast cancer, for which treatment with tamoxifen is indicated; 2. Use of tamoxifen for at least 4 weeks (to guarantee steady-state); 3. Concomitant use of paroxetine for at least 4 weeks; 4. Age > 18 years; 5. WHO performance < 1; 6. Adequate renal and hepatic functions; 7. Adequate hematological blood counts; 8. Written informed consent; 9. No radiotherapy or chemotherapy within the last 4 weeks before start; 10. No concurrent (over the counter) medication or (herbal) supplements, except SSRIs, known to induce or inhibit CYP2D6, CYP2C, CYP3A4 and/or P-glycoprotein; 11. No concurrent medication or supplements which can interact with venlafaxine and/or escitalopram; 12. Abstain from grapefruit, grapefruit juice, herbal dietary supplements, and herbal tea during the study.
Exclusion criteria
Exclusion criteria: 1. Pregnant or lactating patients; 2. Serious illness or medical unstable condition requiring treatment, symptomatic CNSmetastases or history of psychiatric disorder that would prohibit the understanding and giving of informed consent; 3. Patients with a history of suicide attempts or current suicidal ideation; 4. Contra-indications for venlafaxine and/or escitalopram use; 5. Patients with Congenital Long QT Syndrome (CLQTS); 6. Use of medications or dietary supplements, except SSRIs, known to induce or inhibit CYP2D6, CYP2C, CYP3A4 and/or P-glycoprotein; 7. More than one dose of tamoxifen (20 or 40 mg) per day; 8. Non-compliance.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Determine the effects of switching from the potent CYP2D6 inhibitor paroxetine to a weak CYP2D6 inhibitor (venlafaxine, escitalopram) on the plasma pharmacokinetics of tamoxifen and its metabolites (AUC, CL, Cmax). | — |
Secondary
| Measure | Time frame |
|---|---|
| Compare toxic adverse effects in treatment courses with tamoxifen before and after switching from a potent CYP2D6 inhibitor to a weak CYP2D6 inhibitor. | — |
Contacts
Public ContactLisette Binkhorst
Groene Hilledijk 301
Outcome results
None listed