Determination of a radotinib dosage regimen based on dose–response relationships for the treatment of newly diagnosed patients with chronic myeloid leukemia
Abstract Radotinib is a second‐generation BCR‐ABL1 tyrosine kinase inhibitor approved for the treatment of chronic myeloid leukemia in chronic phase (CP‐CML). Here, using the data from a Phase 3 study conducted in patients with newly diagnosed CP‐CML, the dose–efficacy as well as dose–safety relatio...
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| Format: | Article |
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Wiley
2018-05-01
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| Series: | Cancer Medicine |
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| Online Access: | https://doi.org/10.1002/cam4.1436 |
| _version_ | 1811154941950033920 |
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| author | Hayeon Noh Su Young Jung Jae‐Yong Kwak Sung‐Hyun Kim Suk Joong Oh Dae Young Zang Suhyun Lee Hye Lin Park Dae Jin Jo Jae Soo Shin Young Rok Do Dong‐Wook Kim Jangik I. Lee |
| author_facet | Hayeon Noh Su Young Jung Jae‐Yong Kwak Sung‐Hyun Kim Suk Joong Oh Dae Young Zang Suhyun Lee Hye Lin Park Dae Jin Jo Jae Soo Shin Young Rok Do Dong‐Wook Kim Jangik I. Lee |
| author_sort | Hayeon Noh |
| collection | DOAJ |
| description | Abstract Radotinib is a second‐generation BCR‐ABL1 tyrosine kinase inhibitor approved for the treatment of chronic myeloid leukemia in chronic phase (CP‐CML). Here, using the data from a Phase 3 study conducted in patients with newly diagnosed CP‐CML, the dose–efficacy as well as dose–safety relationship analyses were performed to determine a safe and effective initial dosage regimen of radotinib. A significant positive association was detected between the starting dose of radotinib adjusted for body weight (Dose/BW) and the probability of dose‐limiting toxicity (≥grade 3 hematologic and nonhematologic toxicity) (P = 0.003). In contrast, a significant inverse association was discovered between Dose/BW and the probability of major molecular response (BCR‐ABL1/ABL1 ≤ 0.1%) when controlled for sex (P = 0.033). Moreover, frequent dose interruptions and reductions secondary to radotinib toxicities occurred in the Phase 3 study, resulting in nearly half (44%) of patients receiving a reduced dose at a 12‐month follow‐up. In conclusion, the results of this study demonstrate the need for initial radotinib dose attenuation to improve the long‐term efficacy and safety of radotinib. Hence, the authors suggest a new upfront radotinib dose of 400 mg once daily be tested in patients with newly diagnosed CP‐CML. |
| first_indexed | 2024-04-10T04:24:37Z |
| format | Article |
| id | doaj.art-0adbe5088461456394a1507cc1d1acc6 |
| institution | Directory Open Access Journal |
| issn | 2045-7634 |
| language | English |
| last_indexed | 2024-04-10T04:24:37Z |
| publishDate | 2018-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj.art-0adbe5088461456394a1507cc1d1acc62023-03-10T15:42:21ZengWileyCancer Medicine2045-76342018-05-01751766177310.1002/cam4.1436Determination of a radotinib dosage regimen based on dose–response relationships for the treatment of newly diagnosed patients with chronic myeloid leukemiaHayeon Noh0Su Young Jung1Jae‐Yong Kwak2Sung‐Hyun Kim3Suk Joong Oh4Dae Young Zang5Suhyun Lee6Hye Lin Park7Dae Jin Jo8Jae Soo Shin9Young Rok Do10Dong‐Wook Kim11Jangik I. Lee12Department of Pharmacy College of Pharmacy Yonsei University Incheon KoreaDepartment of Pharmacy College of Pharmacy Seoul National University Seoul KoreaChonbuk National University Medical School & Hospital Jeonju KoreaDepartment of Internal Medicine Dong‐A University College of Medicine Busan KoreaDepartment of Internal Medicine Kangbuk Samsung Hospital Sungkyunkwan University School of Medicine Seoul KoreaDepartment of Internal Medicine Hallym University Sacred Heart Hospital Anyang KoreaDepartment of Pharmacy College of Pharmacy Seoul National University Seoul KoreaCentral Research Institute IL‐YANG Pharmaceutical Co., Ltd. Yongin KoreaCentral Research Institute IL‐YANG Pharmaceutical Co., Ltd. Yongin KoreaCentral Research Institute IL‐YANG Pharmaceutical Co., Ltd. Yongin KoreaDepartment of Medicine Dongsan Medical Center Keimyung University Daegu KoreaSeoul St. Mary's Hospital Leukemia Research Institute The Catholic University of Korea Seoul KoreaDepartment of Pharmacy College of Pharmacy Seoul National University Seoul KoreaAbstract Radotinib is a second‐generation BCR‐ABL1 tyrosine kinase inhibitor approved for the treatment of chronic myeloid leukemia in chronic phase (CP‐CML). Here, using the data from a Phase 3 study conducted in patients with newly diagnosed CP‐CML, the dose–efficacy as well as dose–safety relationship analyses were performed to determine a safe and effective initial dosage regimen of radotinib. A significant positive association was detected between the starting dose of radotinib adjusted for body weight (Dose/BW) and the probability of dose‐limiting toxicity (≥grade 3 hematologic and nonhematologic toxicity) (P = 0.003). In contrast, a significant inverse association was discovered between Dose/BW and the probability of major molecular response (BCR‐ABL1/ABL1 ≤ 0.1%) when controlled for sex (P = 0.033). Moreover, frequent dose interruptions and reductions secondary to radotinib toxicities occurred in the Phase 3 study, resulting in nearly half (44%) of patients receiving a reduced dose at a 12‐month follow‐up. In conclusion, the results of this study demonstrate the need for initial radotinib dose attenuation to improve the long‐term efficacy and safety of radotinib. Hence, the authors suggest a new upfront radotinib dose of 400 mg once daily be tested in patients with newly diagnosed CP‐CML.https://doi.org/10.1002/cam4.1436Chronic myeloid leukemiadose determinationdose–response relationshipradotinibtyrosine kinase inhibitor |
| spellingShingle | Hayeon Noh Su Young Jung Jae‐Yong Kwak Sung‐Hyun Kim Suk Joong Oh Dae Young Zang Suhyun Lee Hye Lin Park Dae Jin Jo Jae Soo Shin Young Rok Do Dong‐Wook Kim Jangik I. Lee Determination of a radotinib dosage regimen based on dose–response relationships for the treatment of newly diagnosed patients with chronic myeloid leukemia Cancer Medicine Chronic myeloid leukemia dose determination dose–response relationship radotinib tyrosine kinase inhibitor |
| title | Determination of a radotinib dosage regimen based on dose–response relationships for the treatment of newly diagnosed patients with chronic myeloid leukemia |
| title_full | Determination of a radotinib dosage regimen based on dose–response relationships for the treatment of newly diagnosed patients with chronic myeloid leukemia |
| title_fullStr | Determination of a radotinib dosage regimen based on dose–response relationships for the treatment of newly diagnosed patients with chronic myeloid leukemia |
| title_full_unstemmed | Determination of a radotinib dosage regimen based on dose–response relationships for the treatment of newly diagnosed patients with chronic myeloid leukemia |
| title_short | Determination of a radotinib dosage regimen based on dose–response relationships for the treatment of newly diagnosed patients with chronic myeloid leukemia |
| title_sort | determination of a radotinib dosage regimen based on dose response relationships for the treatment of newly diagnosed patients with chronic myeloid leukemia |
| topic | Chronic myeloid leukemia dose determination dose–response relationship radotinib tyrosine kinase inhibitor |
| url | https://doi.org/10.1002/cam4.1436 |
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