The recommended starting dose of
bosutinib is 500 mg/day for chronic-phase (CP) or accelerated-/
blast-phase Philadelphia chromosome-positive (Ph+)
chronic myeloid leukemia (CML) resistant/intolerant to prior
therapy. However, some patients may require
dose reductions to manage the occurrences of adverse events (AEs).
Bosutinib efficacy and safety were evaluated following
dose reductions in a phase I/II study of Ph+ patients with CP CML resistant/intolerant to
imatinib or
imatinib plus
dasatinib and/or
nilotinib, and those with accelerated-/
blast-phase CML or
acute lymphoblastic leukemia after at least
imatinib treatment. In all, 570 patients with ≥4 years' follow-up were included in this analysis. Among 144 patients who dose-reduced to
bosutinib 400 mg/day (without reduction to 300 mg/day), 22 (15 %) had complete cytogenetic response (CCyR) before and after reduction, 40 (28 %) initially achieved CCyR after reduction, and 4 (3 %) only had CCyR before reduction. Among 95 patients who dose-reduced to
bosutinib 300 mg/day, 23 (24 %) had CCyR before and after reduction, 13 (14 %) initially achieved CCyR after reduction, and 3 (3 %) only had CCyR before reduction. Results were similar to matched controls who remained on 500 mg/day, indicating
dose reductions had not substantially affected efficacy. The incidence of treatment-emergent AEs was lower after
dose reductions, particularly for gastrointestinal events. The incidence of hematologic toxicities generally was similar before and after
dose reduction. The management of AEs with
bosutinib through
dose reduction can lead to improved/maintained efficacy and better tolerability; still, approximately half of patients on treatment at year 4 maintained a dose of ≥500 mg/day. ClinicalTrials.gov: NCT00261846.