Breast cancer
Conditions
Interventions
Patients will be switched from paroxetine (potent CYP2D6 inhibitor) to
treatment with a weak CYP2D6 inhibiting antidepressant (venlafaxine or
escitalopram).
Amendment: Patients will be switched fr
Sponsors
Erasmus MC, Universitair Medisch Centrum Rotterdam
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: - Histological or cytological confirmed diagnosis of breast cancer, for which treatment with tamoxifen is indicated (to be evaluated by the treating physician); - Use of tamoxifen for at least 4 weeks (to guarantee steady-state) and willing to continue the treatment until the end of the study; - Concomitant use of paroxetine for at least 4 weeks (Amendment: or other antidepressant which has been shown to inhibit CYP2D6 in vitro/in vivo); - Age > 18 years; - WHO performance
Exclusion criteria
Exclusion criteria: - Pregnant or lactating patients; - Serious illness or medical unstable condition requiring treatment, symptomatic CNS-metastases or history of psychiatric disorder that would prohibit the understanding and giving of informed consent; - Patients with a history of suicide attempts or current suicidal ideation; - Contra-indications for venlafaxine and/or escitalopram use; - Patients with Congenital Long QT Syndrome (CLQTS); - Use of medications or dietary supplements known to induce or inhibit CYP2D6, CYP2C, CYP3A4 and/or P-glycoprotein; - Unwillingness to abstain from grapefruit (juice), (herbal) dietary supplements, herbals, over-the-counter medication (except for paracetamol); - More than one dose of tamoxifen (20 or 40 mg) per day; - Non-compliance.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| - To determine the effects of switching from the potent CYP2D6 inhibitor paroxetine to a weak CYP2D6 inhibitor (venlafaxine, escitalopram) on the metabolism and plasma pharmacokinetics of tamoxifen and its metabolites in breast cancer patients on tamoxifen therapy. Pharmacokinetic parameters to be determined will include clearance (CL), area under the plasma-concentration time curves (AUC), the maximum concentration (Cmax) and time of Cmax (tmax). | — |
Secondary
| Measure | Time frame |
|---|---|
| - To compare toxic adverse effects in treatment courses with tamoxifen before and after switching from a potent CYP2D6 inhibitor to a weak CYP2D6 inhibitor (changes in adverse effects, severity of adverse effects). Amendment: Tertiary study parameters/outcome: - To study the influence of antidepressants, other than paroxetine, which have been shown to inhibit CYP2D6 in vitro and/or in vivo, on the pharmacokinetics of tamoxifen (patient cases). Pharmacokinetic parameters to be determined will include clearance (CL), area under the plasma-concentration time curves (AUC), the maximum concentration (Cmax) and time of Cmax (tmax). | — |
Countries
Netherlands
Outcome results
None listed