The literature indicates that a minimal endoxifen concentration of 16 nmol/L is needed to produce a therapeutic effect. This implies that the endoxifen levels in individual patients must stay above this threshold throughout the entire treatment…
ID
Bron
Aandoening
Adjuvante behandeling van oestrogeenreceptor positieve (HR+) borstkanker.
Ondersteuning
Onderzoeksproduct en/of interventie
Uitkomstmaten
Primaire uitkomstmaten
To prove that TDM of tamoxifen is feasible in clinical practice.
Achtergrond van het onderzoek
As a prodrug, tamoxifen is susceptible to metabolism by the cytochrome P450 enzyme system. The most active metabolite created in this process is endoxifen. Adjuvant treatment with tamoxifen significantly reduces the chance of recurrence. Nevertheless, the five year recurrence rate in the adjuvant setting after 5-years of tamoxifen treatment is 11-23%, depending on nodal status and prior chemotherapy. The literature indicates that a minimal endoxifen concentration of 16 nmol/L is needed to produce a therapeutic effect. This implies that the endoxifen levels in individual patients must stay above this threshold throughout the entire treatment period. Factors that could contribute to endoxifen levels include: non-compliance with treatment regime, co-medication, advanced age, low BMI, genotype and phenotype. Several studies have demonstrated that the endoxifen levels of tamoxifen varied greatly in patients administrated with the same daily dose tamoxifen. Because of the wide intra-patient variability in drug exposure due to differences in pharmacokinetics of tamoxifen, optimal dose seems to be a problem in 20-30% of the patients. Therapeutic Drug Monitoring can in those cases be a useful tool for physicians managing patients with tamoxifen treatment.The aim of this process is to individualize therapeutic regimens for optimal patient benefit. The important question is whether TDM guided dose individualization is also feasible in large patient groups. In this exploratory study we will therefore evaluate the impact of TDM guided dosing on endoxifen levels in patients with breast cancer, treated with tamoxifen.
Doel van het onderzoek
The literature indicates that a minimal endoxifen concentration of 16 nmol/L is needed to produce a therapeutic effect. This implies that the endoxifen levels in individual patients must stay above this threshold throughout the entire treatment period. Factors that could contribute to endoxifen levels include: non-compliance with treatment regime, co-medication, advanced age, low BMI, genotype and phenotype. Several studies have demonstrated that the endoxifen levels of tamoxifen varied greatly in patients administrated with the same daily dose tamoxifen. Because of the wide intra-patient variability in drug exposure due to differences in pharmacokinetics of tamoxifen, optimal dose seems to be a problem in 20-30% of the patients. Therapeutic Drug Monitoring can in those cases be a useful tool for physicians managing patients with tamoxifen treatment. The aim of this process is to individualize therapeutic regimens for optimal patient benefit.
Onderzoeksopzet
Patients will be seen in the outpatient clinic for pharmacokinetic blood sampling (Therapeutic Drug Monitoring of tamoxifen) on months 3, 6, 12, 18 and 24 after start with tamoxifen treatment.
Onderzoeksproduct en/of interventie
TDM guided dosage modifications are allowed during the study period. Start dosing tamoxifen 20 mg once daily, thereafter dosing advices based on blood concentration endoxifen.
Publiek
Louwrens Braal
Erasmus University Medical Center, Department of Medical Oncology ‘s Gravendijkwal 230
Rotterdam 3015 CE
The Netherlands
+ 31 0(10)41112
c.braal@erasmusmc.nl
Wetenschappelijk
Louwrens Braal
Erasmus University Medical Center, Department of Medical Oncology ‘s Gravendijkwal 230
Rotterdam 3015 CE
The Netherlands
+ 31 0(10)41112
c.braal@erasmusmc.nl
Belangrijkste voorwaarden om deel te mogen nemen (Inclusiecriteria)
1. Adult women (≥ 18 years of age) who are planned to start adjuvant tamoxifen therapy.
2. WHO Performance Status ≤ 1
3. Able and willing to sign the Informed Consent Form prior to screening evaluations
4. Able and willing to undergo blood sampling for PK analysis.
Belangrijkste redenen om niet deel te kunnen nemen (Exclusiecriteria)
1. Woman who are pregnant or breast feeding;
2. Endometrial cancer (diagnosis < 3 years ago)
3. Symptomatic CNS metastases or history of psychiatric disorder that would prohibit the
understanding and giving of informed consent.
4. Patients with known alcoholism, drug addiction and/or psychiatric of physiological
condition which in the opinion of the investigator would impair treatment compliance.
5. Evidence of any other disease, neurological or metabolic dysfunction, physical
examination finding or laboratory finding giving reasonable suspicion of a disease or
condition that contraindicates the use of tamoxifen or puts the patient at high risk for
treatment related complications.
6. 3 months tamoxifen treatment
Opzet
Deelname
Voornemen beschikbaar stellen Individuele Patiënten Data (IPD)
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Andere (mogelijk minder actuele) registraties in dit register
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In overige registers
| Register | ID |
|---|---|
| NTR-new | NL6918 |
| NTR-old | NTR7113 |
| Ander register | METC Erasmus MC : MEC 17-548 // NL.63787.078.17 |