Determination of a radotinib dosage regimen based on dose-response relationships for the treatment of newly diagnosed patients with chronic myeloid leukemiaopen access
- Authors
- Noh, Hayeon; Jung, Su Young; Kwak, Jae-Yong; Kim, Sung-Hyun; Oh, Suk Joong; Zang, Dae Young; Lee, Suhyun; Park, Hye Lin; Jo, Dae Jin; Shin, Jae Soo; Do, Young Rok; Kim, Dong-Wook; Lee, Jangik, I
- Issue Date
- May-2018
- Publisher
- WILEY
- Keywords
- Chronic myeloid leukemia; dose determination; dose-response relationship; radotinib; tyrosine kinase inhibitor
- Citation
- CANCER MEDICINE, v.7, no.5, pp.1766 - 1773
- Indexed
- SCIE
SCOPUS
- Journal Title
- CANCER MEDICINE
- Volume
- 7
- Number
- 5
- Start Page
- 1766
- End Page
- 1773
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/191500
- DOI
- 10.1002/cam4.1436
- ISSN
- 2045-7634
- 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.
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