CYP2D6 Genotypes and Breast Cancer Clinical Outcomes in the Indonesian Population
Study Details
Study Description
Brief Summary
The utilization of tamoxifen is considerably high in Indonesia, with about 170,000 tamoxifen prescriptions filed in 2015. It is metabolized by the enzyme CYP2D6, resulting in its active metabolite, endoxifen, which has been proven to be effective in the prevention and treatment of breast cancer.
Studies showed the CYP2D6 gene has more than 100 variants; some of which are linked with reduced drug activity, while others do not have any pathological implications. The metabolizer profile of these variants is generally grouped into Ultra-rapid, Normal, Intermediate, and Poor Metabolizers (UM, NM, IM, and PM, respectively). In our previous study (NCT04312347), the investigators recruited 150 breast cancer patients who were taking adjusted dose of tamoxifen daily based on their CYP2D6 phenotype. Although the investigators have measured the endoxifen level of the patients with adjusted treatment, the clinical outcomes of the study are not yet conclusive.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| N/A |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Dose adjustment of tamoxifen Following the CPIC guidelines, those identified as Poor Metabolizers (PMs) and Intermediate Metabolizers (IMs) from our previous study are recommended to adjust their tamoxifen dosage to 40 mg per day. |
Drug: Tamoxifen
Suggesting an increase in the dose of tamoxifen to those who have suboptimum level of endoxifen due to their genetic variations
|
| No Intervention: Standard dose of tamoxifen Those identified as Normal Metabolizers (NMs) from our previous study remain on tamoxifen 20 mg per day. |
Outcome Measures
Primary Outcome Measures
- Overall Survival rate [3 year]
The percentage of study participants who are still alive by the end of this study after being diagnosed with breast cancer
- Progression Survival rate [3 year]
The percentage of study participants who live with the disease but the disease does not get worse by the end of this study
Other Outcome Measures
- Long-term side effects of tamoxifen [3 year]
Long-term side effects of tamoxifen, including heartburn, thromboembolic event, endometrial hyperplasia and uterine cancer, will also be monitored and documented using the Adverse Drug Reaction (ADR) reporting form provided by the Indonesian National Agency of Drug and Food Control.
Eligibility Criteria
Criteria
Inclusion Criteria:
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female
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diagnosed with ER+ breast cancer
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have been genotyped and classified as PM and IM in the previous study
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are recommended by doctor to take tamoxifen 40 mg according to their metabolizer profile
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have finished the definitive therapy course (surgery, chemotherapy, or radiotherapy).
Exclusion Criteria:
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have other primary cancer aside from breast cancer.
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those with residual tumor cells/have experienced second primary breast tumor.
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patients who are recommended by doctor to switch to aromatase inhibitors (AI)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | MRCCC Siloam Hospitals Semanggi | Jakarta | DKI Jakarta | Indonesia | 12930 |
Sponsors and Collaborators
- Nalagenetics Pte Ltd
- SJH Initiatives
- Indonesia University
- MRCCC Siloam Hospitals Semanggi
Investigators
- Study Chair: Baitha Maggadani, MPharm, Fakultas Farmasi Universitas Indonesia
- Study Chair: Arief Winata, MD, MRCCC Siloam Hospitals Semanggi
- Principal Investigator: Samuel Haryono, MD, PhD, SJH Innitiatives
- Study Chair: Fatma Aldila, PharmD, Nalagenetics Pte Ltd
Study Documents (Full-Text)
None provided.More Information
Publications
- Braal CL, Jager A, Hoop EO, Westenberg JD, Lommen KMWT, de Bruijn P, Vastbinder MB, van Rossum-Schornagel QC, Thijs-Visser MF, van Alphen RJ, Struik LEM, Zuetenhorst HJM, Mathijssen RHJ, Koolen SLW. Therapeutic Drug Monitoring of Endoxifen for Tamoxifen Precision Dosing: Feasible in Patients with Hormone-Sensitive Breast Cancer. Clin Pharmacokinet. 2022 Apr;61(4):527-537. doi: 10.1007/s40262-021-01077-z. Epub 2021 Nov 17.
- Lu J, Li H, Guo P, Shen R, Luo Y, Ge Q, Shi W, Li Y, Zhu W. The effect of CYP2D6 *10 polymorphism on adjuvant tamoxifen in Asian breast cancer patients: a meta-analysis. Onco Targets Ther. 2017 Nov 13;10:5429-5437. doi: 10.2147/OTT.S149197. eCollection 2017.
- Sanchez-Spitman A, Dezentjé V, Swen J, Moes DJAR, Böhringer S, Batman E, van Druten E, Smorenburg C, van Bochove A, Zeillemaker A, Jongen L, Los M, Neven P, Gelderblom H, Guchelaar HJ. Tamoxifen Pharmacogenetics and Metabolism: Results From the Prospective CYPTAM Study. J Clin Oncol. 2019 Mar 10;37(8):636-646. doi: 10.1200/JCO.18.00307. Epub 2019 Jan 24.
- ID-TMS-02-20201012