Serial evaluation of the pharmacokinetics of ponatinib in patients with CML and Ph + ALL
| Autor: | Masatomo Miura, Taro Tochigi, Takashi Nakaike, Shinya Kimura, Kiyoshi Yamashita, Naoto Takahashi, Ikuo Kikuchi, Noriaki Kawano, Koichi Mashiba |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Adult
Male Oncology medicine.medical_specialty Fusion Proteins bcr-abl chemistry.chemical_compound Maintenance therapy Leukemia Myelogenous Chronic BCR-ABL Positive hemic and lymphatic diseases Internal medicine medicine Humans Molecular Targeted Therapy Protein Kinase Inhibitors Aged business.industry Ponatinib Hematopoietic Stem Cell Transplantation Imidazoles Myeloid leukemia Imatinib Hematology Middle Aged Precursor Cell Lymphoblastic Leukemia-Lymphoma Combined Modality Therapy Pyridazines Dasatinib Treatment Outcome chemistry Nilotinib Leukemia Myeloid Chronic-Phase Female Drug Monitoring business Tyrosine kinase Bosutinib medicine.drug |
| Zdroj: | International Journal of Hematology. 114:509-516 |
| ISSN: | 1865-3774 0925-5710 |
| DOI: | 10.1007/s12185-021-03186-8 |
| Popis: | Although tyrosine kinase inhibitors (TKIs) play a crucial role in the treatment of chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL), intolerance and resistance to TKIs have been serious problems. Due to a lack of research, the importance of the pharmacokinetics (PK) of TKIs is currently unclear. We examined the PK of the third-generation TKI ponatinib to monitor side effects and efficacy during treatments for one patient with CML-chronic phase (CP-CML) and two who received allogeneic hematopoietic stem cell transplantation (allo-HSCT), one for CML-blastic crisis (BC-CML) and one for Ph + ALL. The patient with CP-CML was intolerant to multiple TKIs (dasatinib, nilotinib, imatinib, and bosutinib) and thus was switched to ponatinib (15 mg/day). The patients who received allo-HSCT for BC-CML and Ph + ALL received ponatinib (15 mg/day) as maintenance therapy. Notably, serial evaluation of the PK of ponatinib showed that the median trough values (ng/ml) were 17.2 (12.2-34.5), 33.1 (21.2-40.3) and 27.7 (13.6-29.9) in patients 1, 2, and 3, respectively. These values were around the target concentration (23 ng/ml). All patients are maintaining complete remission without side effects. In conclusion, serial evaluation of PK of ponatinib may yield meaningful information about its safety and efficacy. |
| Databáze: | OpenAIRE |
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