Bosutinib

DOSE ESCALATION: in adults resistant or intolerant to prior therapy, the dose may be escalated to 600 mg once daily for unsatisfactory response or signs of progression, in the absence of Grade 3 or 4 or persistent Grade 2 adverse events. In newly-diagnosed chronic phase CML, escalate in 100 mg increments to a maximum of 600 mg once daily if BCR-ABL transcripts are not 10% or less at month 3, provided there is no Grade 3 or 4 adverse reaction and all Grade 2 non-haematological toxicities have resolved to at least Grade 1. PAEDIATRIC (body-surface-area based, NOT per kg): recommended dosage 300 mg/m2 BSA orally once daily for newly-diagnosed chronic phase Ph+ CML and 400 mg/m2 BSA orally once daily for patients resistant or intolerant to prior therapy. SPC Table 1 bands: BSA 0.55 to less than 0.63 m2 — 200 mg (newly diagnosed) / 250 mg (resistant or intolerant); 0.63 to less than 0.75 m2 — 200 mg / 300 mg; 0.75 to less than 0.9 m2 — 250 mg / 350 mg; 0.9 to less than 1.1 m2 — 300 mg / 400 mg; 1.1 m2 or more — 400 mg / 500 mg (maximum starting dose). Maximum paediatric dose is 600 mg once daily in previously treated CML and 500 mg once daily in newly-diagnosed CML. Safety and efficacy below 1 year of age are not established and data below 6 years of age are too limited for a dose recommendation. TOXICITY MODIFICATIONS: for clinically significant moderate or severe non-haematological toxicity, interrupt and resume at a dose reduced by 100 mg once daily after resolution; re-escalation may be considered if clinically appropriate. Doses less than 300 mg/day have been used but efficacy is not established. LIVER: if transaminases rise above 5 x ULN, interrupt until recovery to 2.5 x ULN or less and resume at 400 mg once daily; consider discontinuation if recovery takes longer than 4 weeks; discontinue if transaminases 3 x ULN or more occur with bilirubin above 2 x ULN and alkaline phosphatase below 2 x ULN. DIARRHOEA: for CTCAE Grade 3 to 4 diarrhoea interrupt and resume at 400 mg once daily on recovery to Grade 1 or less. HAEMATOLOGICAL: for ANC below 1.0 x 10^9/L and/or platelets below 50 x 10^9/L, hold until ANC 1.0 x 10^9/L or more and platelets 50 x 10^9/L or more; resume at the same dose if recovery is within 2 weeks, otherwise reduce by 100 mg in adults (50 mg in paediatric patients with BSA below 1.1 m2) — a further 100 mg (or 50 mg) reduction if cytopenia recurs. MISSED DOSE: if missed by more than 12 hours, do not give an extra dose; take the usual prescribed dose the following day. ELDERLY: no specific dose recommendation, but caution because information is limited. CARDIAC / GI: caution in relevant cardiac disorders and in recent or ongoing clinically significant gastrointestinal disorder (such patients were excluded from clinical studies).