Bosutinib safety and management of toxicity in leukemia patients with resistance or intolerance to imatinib and other tyrosine kinase inhibitors
Standard
Bosutinib safety and management of toxicity in leukemia patients with resistance or intolerance to imatinib and other tyrosine kinase inhibitors. / Kantarjian, Hagop M; Cortes, Jorge E; Kim, Dong-Wook; Khoury, H Jean; Brümmendorf, Tim H; Porkka, Kimmo; Martinelli, Giovanni; Durrant, Simon; Leip, Eric; Kelly, Virginia; Turnbull, Kathleen; Besson, Nadine; Gambacorti-Passerini, Carlo.
in: BLOOD, Jahrgang 123, Nr. 9, 2014, S. 1309-18.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Bosutinib safety and management of toxicity in leukemia patients with resistance or intolerance to imatinib and other tyrosine kinase inhibitors
AU - Kantarjian, Hagop M
AU - Cortes, Jorge E
AU - Kim, Dong-Wook
AU - Khoury, H Jean
AU - Brümmendorf, Tim H
AU - Porkka, Kimmo
AU - Martinelli, Giovanni
AU - Durrant, Simon
AU - Leip, Eric
AU - Kelly, Virginia
AU - Turnbull, Kathleen
AU - Besson, Nadine
AU - Gambacorti-Passerini, Carlo
PY - 2014
Y1 - 2014
N2 - Bosutinib is an oral, dual SRC/ABL tyrosine kinase inhibitor (TKI) with clinical activity in Philadelphia chromosome-positive (Ph(+)) leukemia. We assessed the safety and tolerability of bosutinib 500 mg per day in a phase 1/2 study in chronic-phase (CP) chronic myeloid leukemia (CML) or advanced Ph(+) leukemia following resistance/intolerance to imatinib and possibly other TKIs. Patient cohorts included second-line CP CML (n = 286), third-/fourth-line CP CML (n = 118), and advanced leukemia (n = 166). Median bosutinib duration was 11.1 (range, 0.03-83.4) months. Treatment-emergent adverse events (TEAEs) in each cohort were primarily gastrointestinal (diarrhea [86%/83%/74%], nausea [46%/48%/48%], and vomiting [37%/38%/43%]). Diarrhea presented early, with few (8%) patients experiencing grade 3/4 events; dose reduction due to diarrhea occurred in 6% of affected patients. Grade 3/4 myelosuppression TEAEs were reported in 41% of patients; among affected patients, 46% were managed with bosutinib interruption and 32% with dose reduction. Alanine aminotransferase elevation TEAEs occurred in 17% of patients (grade 3/4, 7%); among patients managed with dose interruption, bosutinib rechallenge was successful in 74%. Bosutinib demonstrated acceptable safety with manageable toxicities in Ph(+) leukemia. This trial (NCT00261846) was registered at www.ClinicalTrials.gov (this manuscript is based on a different data snapshot from that in ClinicalTrials.gov).
AB - Bosutinib is an oral, dual SRC/ABL tyrosine kinase inhibitor (TKI) with clinical activity in Philadelphia chromosome-positive (Ph(+)) leukemia. We assessed the safety and tolerability of bosutinib 500 mg per day in a phase 1/2 study in chronic-phase (CP) chronic myeloid leukemia (CML) or advanced Ph(+) leukemia following resistance/intolerance to imatinib and possibly other TKIs. Patient cohorts included second-line CP CML (n = 286), third-/fourth-line CP CML (n = 118), and advanced leukemia (n = 166). Median bosutinib duration was 11.1 (range, 0.03-83.4) months. Treatment-emergent adverse events (TEAEs) in each cohort were primarily gastrointestinal (diarrhea [86%/83%/74%], nausea [46%/48%/48%], and vomiting [37%/38%/43%]). Diarrhea presented early, with few (8%) patients experiencing grade 3/4 events; dose reduction due to diarrhea occurred in 6% of affected patients. Grade 3/4 myelosuppression TEAEs were reported in 41% of patients; among affected patients, 46% were managed with bosutinib interruption and 32% with dose reduction. Alanine aminotransferase elevation TEAEs occurred in 17% of patients (grade 3/4, 7%); among patients managed with dose interruption, bosutinib rechallenge was successful in 74%. Bosutinib demonstrated acceptable safety with manageable toxicities in Ph(+) leukemia. This trial (NCT00261846) was registered at www.ClinicalTrials.gov (this manuscript is based on a different data snapshot from that in ClinicalTrials.gov).
KW - Adolescent
KW - Adult
KW - Aged
KW - Aged, 80 and over
KW - Aniline Compounds
KW - Benzamides
KW - Dose-Response Relationship, Drug
KW - Drug Resistance, Neoplasm
KW - Drug-Related Side Effects and Adverse Reactions
KW - Female
KW - Humans
KW - Leukemia, Myelogenous, Chronic, BCR-ABL Positive
KW - Male
KW - Middle Aged
KW - Nitriles
KW - Piperazines
KW - Protein Kinase Inhibitors
KW - Protein-Tyrosine Kinases
KW - Pyrimidines
KW - Quinolines
KW - Withholding Treatment
KW - Young Adult
U2 - 10.1182/blood-2013-07-513937
DO - 10.1182/blood-2013-07-513937
M3 - SCORING: Journal article
C2 - 24345751
VL - 123
SP - 1309
EP - 1318
JO - BLOOD
JF - BLOOD
SN - 0006-4971
IS - 9
ER -