Open AccessDetermination of a radotinib dosage regimen based on dose–response relationships for the treatment of newly diagnosed patients with chronic myeloid leukemia
Author(s) -
Noh Hayeon,
Jung Su Young,
Kwak JaeYong,
Kim SungHyun,
Oh Suk Joong,
Zang Dae Young,
Lee Suhyun,
Park Hye Lin,
Jo Dae Jin,
Shin Jae Soo,
Do Young Rok,
Kim DongWook,
Lee Jangik I.
Publication year - 2018
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.1436
Subject(s) - medicine , regimen , myeloid leukemia , toxicity , tyrosine kinase inhibitor , gastroenterology , chemotherapy , cancer
Radotinib is a second‐generation BCR ‐ ABL 1 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 ‐ ABL 1/ ABL 1 ≤ 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 .