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).

Kantarjian, H., Cortes, J., Kim, D., Khoury, H., Brümmendorf, T., Porkka, K., et al. (2013). Bosutinib safety and management of toxicity in leukemia patients with resistance or intolerance to imatinib and other tyrosine kinase inhibitors. BLOOD, 123(9), 1309-1318 [10.1182/blood-2013-07-513937].

Bosutinib safety and management of toxicity in leukemia patients with resistance or intolerance to imatinib and other tyrosine kinase inhibitors

GAMBACORTI PASSERINI, CARLO
2013

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).
Articolo in rivista - Articolo scientifico
Young Adult; Dose-Response Relationship, Drug; Drug-Related Side Effects and Adverse Reactions; Humans; Aniline Compounds; Protein-Tyrosine Kinases; Aged; Drug Resistance, Neoplasm; Benzamides; Protein Kinase Inhibitors; Nitriles; Piperazines; Pyrimidines; Aged, 80 and over; Adult; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Middle Aged; Withholding Treatment; Quinolines; Adolescent; Female; Male
English
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Kantarjian, H., Cortes, J., Kim, D., Khoury, H., Brümmendorf, T., Porkka, K., et al. (2013). Bosutinib safety and management of toxicity in leukemia patients with resistance or intolerance to imatinib and other tyrosine kinase inhibitors. BLOOD, 123(9), 1309-1318 [10.1182/blood-2013-07-513937].
Kantarjian, H; Cortes, J; Kim, D; Khoury, H; Brümmendorf, T; Porkka, K; Martinelli, G; Durrant, S; Leip, E; Kelly, V; Turnbull, K; Besson, N; GAMBACORTI PASSERINI, C
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/52077
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