title: Bosutinib shows low cross intolerance, in chronic myeloid leukemia patients treated in fourth line. Results of the Spanish compassionate use program.
abstract: The role of bosutinib as rescue treatment of Philadelphia chromosome-positive chronic myeloid leukemia (CML) patients after failing three previous tyrosine kinase inhibitors (TKIs) is currently unknown. We report here the largest series (to our knowledge) of patients treated with bosutinib in fourth-line, after retrospectively reviewing 30 patients in chronic phase, and pretreated with imatinib, nilotinib, and dasatinib. With a median follow up of 11.1 months, the probability to either maintain or improve their CCyR response was 56.6% (17/30) and 11 patients (36.7%) achieved or maintained their baseline MMR. In patients not having baseline CCyR, the probabilities of obtaining CCyR, MMR, and MR4.5 were 13, 11, and 14%, respectively. The probabilities of obtaining MMR and deep molecular response MR4.5 in patients with baseline CCyR were 40.0% (6/15) and 20.0% (3/15). At 20 months, progression-free survival was 73%. Grade 3-4 hematological toxicities were more frequent in resistant than intolerant patients (45.4 vs. 0.0%). Nonhematological toxicities were also more frequent in resistant patients, being diarrhea the most conspicuous one. Bosutinib seems to be an appropriate treatment option for patients resistant or intolerant to three prior TKI's.
authors: Servicio De Hematología, Hospital Universitario Ramón Y Cajal, Madrid, Spain.
authors: Valentín
authors: V
authors: García-Gutiérrez
authors: Alejandra
authors: A
authors: Martinez-Trillos
authors: Jose Luis
authors: JL
authors: Lopez Lorenzo
authors: Guiomar
authors: G
authors: Bautista
authors: Maria Luisa
authors: ML
authors: Martin Mateos
authors: Alberto
authors: A
authors: Alvarez-Larrán
authors: Ana
authors: A
authors: Iglesias Pérez
authors: Andrés
authors: A
authors: Romo Collado
authors: Angeles
authors: A
authors: Fernandez
authors: Angeles
authors: A
authors: Portero
authors: Beatriz
authors: B
authors: Cuevas
authors: Concepción
authors: C
authors: Ruiz
authors: Esperanza
authors: E
authors: Romero
authors: Fernando
authors: F
authors: Ortega
authors: Isabel
authors: I
authors: Mata
authors: José
authors: J
authors: Tallón
authors: Maria Del Carmen
authors: Mdel C
authors: García Garay
authors: María José
authors: MJ
authors: Ramirez Sánchez
authors: Natalia
authors: N
authors: de Las Heras
authors: Pilar
authors: P
authors: Giraldo
authors: Sabela
authors: S
authors: Bobillo
authors: José María
authors: JM
authors: Guinea
authors: Guillermo
authors: G
authors: Deben
authors: Sandra
authors: S
authors: Valencia
authors: Ana
authors: A
authors: Sebrango
authors: Concepción
authors: C
authors: Boqué
authors: Begoña
authors: B
authors: Maestro
authors: Juan Luis
authors: JL
authors: Steegmann
mesh_terms: D000328:Adult; D000368:Aged; D000814:Aniline Compounds / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides / Q000627:therapeutic use; D057176:Compassionate Use Trials; D000069439:Dasatinib; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D015466:Leukemia, Myeloid, Chronic-Phase / Q000188:drug therapy* / Q000201:enzymology / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009570:Nitriles / Q000627:therapeutic use*; D010879:Piperazines / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011743:Pyrimidines / Q000627:therapeutic use; D011804:Quinolines / Q000627:therapeutic use*; D012189:Retrospective Studies; D013030:Spain; D016019:Survival Analysis; D013844:Thiazoles / Q000627:therapeutic use
chemical_list: D000814:Aniline Compounds; D000970:Antineoplastic Agents; D001549:Benzamides; D009570:Nitriles; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011804:Quinolines; D013844:Thiazoles; C471992:bosutinib; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; C498826:nilotinib; D000069439:Dasatinib