Active Ingredient: Bosutinib
Bosutinib is indicated for the treatment of adult patients with:
For this indication, competent medicine agencies globally authorize below treatments:
Oral
400 - 500 mg
From 400 To 500 mg once every day
The recommended dose is 400 mg bosutinib once daily.
The recommended dose is 500 mg bosutinib once daily.
In clinical trials for both indications, treatment with bosutinib continued until disease progression or intolerance to therapy.
In the Phase ½ clinical study in patients with CML who were resistant or intolerant to prior therapy, dose escalations from 500 mg to 600 mg once daily with food were allowed in patients who failed to demonstrate complete haematological response (CHR) by Week 8 or complete cytogenetic response (CCyR) by Week 12 and did not have Grade 3 or higher adverse events possibly-related to the investigational product. Whereas, in the Phase 3 study in patients with newly-diagnosed CP CML treated with bosutinib 400 mg, dose escalations by 100 mg increments to a maximum of 600 mg once daily with food were permitted if the patient failed to demonstrate breakpoint cluster region-Abelson (BCR-ABL) transcripts ≤10% at Month 3, did not have a Grade 3 or 4 adverse reaction at the time of escalation, and all Grade 2 non-haematological toxicities were resolved to at least Grade 1.
In the Phase ½ clinical study in patients with CML who were resistant or intolerant to prior therapy who started treatment at ≤500 mg, 93 (93/558; 16.7%) patients had dose escalations to 600 mg daily.
In the Phase 3 study in patients with newly-diagnosed CP CML who started bosutinib treatment at 400 mg, a total of 46 patients (17.2%) received dose escalations to 500 mg. In addition, 5.6% of patients in the bosutinib treatment group had further dose escalations to 600 mg.
Doses greater than 600 mg/day have not been studied and, therefore, should not be given.
If clinically significant moderate or severe non-haematological toxicity develops, bosutinib should be interrupted, and may be resumed at a dose reduced by 100 mg taken once daily after the toxicity has resolved. If clinically appropriate, re-escalation to the dose prior to the dose reduction taken once daily should be considered. Doses less than 300 mg/day have been used in patients; however, efficacy has not been established.
Elevated liver transaminases: If elevations in liver transaminases >5 × institutional upper limit of normal (ULN) occur, bosutinib should be interrupted until recovery to ≤2.5 × ULN and may be resumed at 400 mg once daily thereafter. If recovery takes longer than 4 weeks, discontinuation of bosutinib should be considered. If transaminase elevations ≥3 × ULN occur concurrently with bilirubin elevations >2 × ULN and alkaline phosphatase <2 × ULN, bosutinib should be discontinued.
Diarrhoea: For NCI Common Terminology Criteria for Adverse Events (CTCAE) Grade 3-4 diarrhoea, bosutinib should be interrupted and may be resumed at 400 mg once daily upon recovery to grade ≤1.
Dose reductions are recommended for severe or persistent neutropenia and thrombocytopenia as described in the following table.
Dose adjustments for neutropenia and thrombocytopenia:
| ANCa <1.0 × 109/L | Hold bosutinib until ANC ≥1.0 × 109/L and platelets ≥50 × 109/L. |
| and/or Platelets <50 × 109/L | Resume treatment with bosutinib at the same dose if recovery occurs within 2 weeks. If blood counts remain low for >2 weeks, upon recovery reduce dose by 100 mg and resume treatment. If cytopoenia recurs, reduce dose by an additional 100 mg upon recovery and resume treatment. Doses less than 300 mg/day have been used; however, efficacy has not been established. |
a ANC = absolute neutrophil count
Bosutinib should be taken orally once daily with food. If a dose is missed by more than 12 hours, the patient should not be given an additional dose. The patient should take the usual prescribed dose on the following day.
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