A tyrosine kinase inhibitor, has been approved by the Food and Drug Administration as a treatment for chronic myeloid leukemia, based on the results of a study of 546 patients.
Trade name Bosulif.
The approved indication is for the treatment of adults with chronic, accelerated, or blast-phase Philadelphia chromosome–positive (Ph+) chronic myeloid leukemia (CML) who are resistant to or cannot tolerate other treatments,
Inhibits the Abl and Src signaling pathways, and is taken once a day at a dose of 500 mg by mouth.
Only two BCR/ABL 1 kinase mutations confirm resistance to bosutinib: the multiresistant T315 I mutations and V299l.
BELA trial phase 3 compared bosutinib to Imatinib with CCyR at 12 months, with identical response rates,70%,
In the international, phase I/II study, all 546 adults enrolled were treated with bosutinib, for chronic, accelerated or blast phase CML, and had progressed after treatment with imatinib or with imatinib followed by dasatinib and/or nilotinib, or they could not tolerate previous treatments (FDA).
Among the patients with chronic phase CML who had been treated previously with imatinib (266 patients), almost 34% achieved a major cytogenic response (MCyR) by 24 weeks of treatment with bosutinib. Almost 53% of the patients who achieved a MCyR had a response that lasted at least 18 months, and a median duration of MCyR was not reached.
Of the 108 patients with chronic phase CML who had been treated with imatinib and at least one other tyrosine kinase inhibitor, almost 27% achieved a MCyR by 24 weeks of treatment with bosutinib.
About 51% of those who achieved a MCyR had a response that lasted at least 9 months, and in this group of patients, the median duration of MCyR also was not reached.
Among patients with accelerated CML, who had been treated previously with a regimen that included at least imatinib, 33% had a complete hematologic response, and 55% achieved an overall hematologic response within the first 48 weeks of treatment.
Among those with blast phase CML, 15% achieved a complete hematologic response, and 28% achieved an overall hematologic response.
Of the total 374 evaluable patients with chronic CML, 16 patients (4%) had confirmed disease transformation to advanced or blast phase while undergoing treatment with bosutinib.
Efficacy comparable with nilotinib and dasatinib In patients with Imatinib resistance.
Diarrhea, nausea, thrombocytopenia, vomiting, abdominal pain, rash, anemia, fever, and fatigue were among the most common adverse events.
Dose:1 orally daily with food