A lower initial dose of bosutinib for patients with chronic myeloid leukemia patients resistant and/or intolerant to prior therapy: a single-arm, multicenter, phase 2 trial (BOGI trial).
Int J Hematol
; 120(4): 492-500, 2024 Oct.
Article
in En
| MEDLINE
| ID: mdl-39136895
ABSTRACT
Although bosutinib is generally safe and effective, drug-related toxicities (DRTs) such as diarrhea or increased transaminase levels often lead to treatment discontinuation. To clarify whether a lower initial dose of bosutinib (i.e., starting at 200 mg) would reduce rates of discontinuation due to DRTs, we conducted a phase 2 study of BOsutinib Gradual Increase (BOGI trial, UMIN 000032282) as a second/third-line treatment for chronic myeloid leukemia (CML). Between February 4, 2019 and May 24, 2022, 35 patients were enrolled. The rate of bosutinib discontinuation at 12 months was 25.7% vs. 35.9% in a historical control study (Japanese phase 1/2 study) (p = 0.102). The rate of bosutinib discontinuation due to DRTs was significantly lower, at 11.4% vs. 28.2% (p = 0.015). The incidence of grade 3/4 transaminase elevation was 20% vs. 29% (p = 0.427), while the incidence of diarrhea was 3% vs. 25% (p = 0.009). The median dose intensity of bosutinib was higher (391.7 mg/day vs. 353.9 mg/day). Pharmacokinetic analysis of bosutinib showed that patients who achieved a major molecular response tended to have high trough concentrations. Thus, a low initial dose of bosutinib followed by dose escalation reduced discontinuation due to severe DRTs while maintaining high dose intensity and efficacy.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Quinolines
/
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
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Aniline Compounds
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Nitriles
Limits:
Adult
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Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Language:
En
Journal:
Int J Hematol
Journal subject:
HEMATOLOGIA
Year:
2024
Document type:
Article
Affiliation country:
Japan
Country of publication:
Japan