Tolerance-based capecitabine dose escalation after DPYD genotype-guided dosing in heterozygote DPYD variant carriers
| Autor: | Ithamar Brinkman, Jelmer J. van Zanden, Jan P. Kleinjan, Robbert Bakema, Johan M. van Rooijen |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Adult
Male 0301 basic medicine Oncology Antimetabolites Antineoplastic Heterozygote Cancer Research medicine.medical_specialty Genotype medicine.medical_treatment Single Center Polymorphism Single Nucleotide Capecitabine 03 medical and health sciences 0302 clinical medicine Neoplasms Internal medicine Dihydropyrimidine dehydrogenase Humans Medicine Pharmacology (medical) Dosing Dihydrouracil Dehydrogenase (NADP) Aged Retrospective Studies Aged 80 and over Pharmacology Chemotherapy business.industry Middle Aged Prognosis Survival Rate 030104 developmental biology 030220 oncology & carcinogenesis Practice Guidelines as Topic Cohort Toxicity Female DPYD business Follow-Up Studies medicine.drug |
| Zdroj: | Anti-Cancer Drugs. 30:410-415 |
| ISSN: | 0959-4973 |
| DOI: | 10.1097/cad.0000000000000748 |
| Popis: | OBJECTIVE Certain polymorphisms of the DPYD gene encoding for the dihydropyrimidine dehydrogenase (DPD) enzyme are associated with fluoropyrimidine-induced toxicity. Dose reductions of the fluoropyrimidine prodrug capecitabine are recommended for patients carrying these DPYD variants to prevent toxicities. Capecitabine dose escalation after an initial genotype-guided dose reduction is advocated when treatment is well tolerated. However, practical guidelines on how to implement these dose escalations are lacking. We implemented a protocol for tolerance-guided capecitabine dosing in DPYD variant carriers and aimed to explore its effect on toxicity of treatment. PATIENTS AND METHODS Patients receiving capecitabine-based chemotherapy for different types of solid tumors were identified retrospectively. Capecitabine doses were reduced in case of a DPYD variant (DPYD*2A, c.2846A>T, DPYD*13, or c.1236G>A) and subsequently adjusted on the basis of tolerance. Outcome was evaluated by clinical chart review and dosing characteristics from the hospital pharmacy. Results were compared with a cohort of capecitabine-treated DPYD wild-type patients. RESULTS Of 185 patients eligible for analysis, 11 patients were heterozygous for a DPYD variant. A median dose escalation of 8.5% was achieved using the prespecified protocol. One DPYD variant carrier experienced a grade 3 toxicity after a dose escalation. Overall, DPYD variant carriers did not experience more, or more severe toxicities than DPYD wild-type patients. The total prevalence of severe toxicities in the wild-type group was 43.1% and is comparable with the literature. CONCLUSION Tolerance-based capecitabine dose escalation did not lead to more toxicity in DPYD variant carriers compared with wild-type patients. Our results can guide future prospective research. |
| Databáze: | OpenAIRE |
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