Research ExplorerPublicationsBosutinib safety and management of toxicity in leukemia pati...

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, Vol. 123, No. 9, 2014, p. 1309-18.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Kantarjian, HM, Cortes, JE, Kim, D-W, Khoury, HJ, Brümmendorf, TH, Porkka, K, Martinelli, G, Durrant, S, Leip, E, Kelly, V, Turnbull, K, Besson, N & Gambacorti-Passerini, C 2014, 'Bosutinib safety and management of toxicity in leukemia patients with resistance or intolerance to imatinib and other tyrosine kinase inhibitors', BLOOD, vol. 123, no. 9, pp. 1309-18. https://doi.org/10.1182/blood-2013-07-513937

APA

Kantarjian, H. M., Cortes, J. E., Kim, D-W., Khoury, H. J., Brümmendorf, T. H., Porkka, K., Martinelli, G., Durrant, S., Leip, E., Kelly, V., Turnbull, K., Besson, N., & Gambacorti-Passerini, C. (2014). Bosutinib safety and management of toxicity in leukemia patients with resistance or intolerance to imatinib and other tyrosine kinase inhibitors. BLOOD, 123(9), 1309-18. https://doi.org/10.1182/blood-2013-07-513937

Vancouver

Kantarjian HM, Cortes JE, Kim D-W, Khoury HJ, Brümmendorf TH, Porkka K et al. Bosutinib safety and management of toxicity in leukemia patients with resistance or intolerance to imatinib and other tyrosine kinase inhibitors. BLOOD. 2014;123(9):1309-18. https://doi.org/10.1182/blood-2013-07-513937

Bibtex

@article{a0d40c83c50a4ae8b2566c08f2babcaf,
title = "Bosutinib safety and management of toxicity in leukemia patients with resistance or intolerance to imatinib and other tyrosine kinase inhibitors",
abstract = "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).",
keywords = "Adolescent, Adult, Aged, Aged, 80 and over, Aniline Compounds, Benzamides, Dose-Response Relationship, Drug, Drug Resistance, Neoplasm, Drug-Related Side Effects and Adverse Reactions, Female, Humans, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Male, Middle Aged, Nitriles, Piperazines, Protein Kinase Inhibitors, Protein-Tyrosine Kinases, Pyrimidines, Quinolines, Withholding Treatment, Young Adult",
author = "Kantarjian, {Hagop M} and Cortes, {Jorge E} and Dong-Wook Kim and Khoury, {H Jean} and Br{\"u}mmendorf, {Tim H} and Kimmo Porkka and Giovanni Martinelli and Simon Durrant and Eric Leip and Virginia Kelly and Kathleen Turnbull and Nadine Besson and Carlo Gambacorti-Passerini",
year = "2014",
doi = "10.1182/blood-2013-07-513937",
language = "English",
volume = "123",
pages = "1309--18",
journal = "BLOOD",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "9",

}

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 -