Bosutinib for the treatment of chronic myeloid leukemia.
OBJECTIVE
The pharmacology, pharmacokinetics, efficacy, and safety of the tyrosine kinase inhibitor (TKI) bosutinib in the management of chronic myeloid leukemia (CML) are reviewed.


CONCLUSIONS
Although clinical outcomes are favorable in patients wth Philadelphia chromosome (Ph)-positive CML who receive first-line TKI therapy with imatinib, dasatinib, and nilotinib, disease progression or relapse may occur. Thus, effective second-line agents are crucial. Bosutinib (Bosulif, Pfizer Inc.) is a second-generation TKI approved for the treatment of patients with Ph-positive chronic-, accelerated-, or blast-phase CML who are intolerant or resistant to other TKIs. Bosutinib inhibits a tyrosine kinase oncogene and Src kinases responsible for CML pathogenesis. Bosutinib is primarily metabolized by cytochrome P-450 (CYP) isoenzyme 3A4; therefore, concomitant use of strong or moderate CYP3A4 inhibitors and inducers should be avoided. Bosutinib is effective in cases involving most imatinib-resistant mutations (not including the T315I and V299L mutations). Clinical trials demonstrated bosutinib's efficacy in inducing durable hematologic and cytogenetic responses, as well as high rates of progression-free and overall survival, in patients with CML who had developed resistance or intolerance to other TKIs. However, bosutinib was not found to be superior to imatinib for inducing cytogenetic responses in cases of newly diagnosed CML and is thus not indicated for use in TKI-naive patients. The most common adverse events among bosutinib-treated patients in clinical trials were diarrhea, nausea, and vomiting, which were generally transient and self-limited.


CONCLUSIONS
Bosutinib is a safe and effective second-line treatment option for select patients with Ph-positive CML who were intolerant or resistant to prior TKI therapy.
Vi Doan, Pharm.D., is Postgraduate Year 2 Oncology Pharmacy Resident; Alice Wang, Pharm.D., BCOP, is Clinical Pharmacy Specialist; and Hillary Prescott, Pharm.D., BCOP, is Clinical Pharmacy Specialist, University of Texas MD Anderson Cancer Center, Houston. vpdoan@mdanderson.org.
Vi
V
Doan
Vi Doan, Pharm.D., is Postgraduate Year 2 Oncology Pharmacy Resident; Alice Wang, Pharm.D., BCOP, is Clinical Pharmacy Specialist; and Hillary Prescott, Pharm.D., BCOP, is Clinical Pharmacy Specialist, University of Texas MD Anderson Cancer Center, Houston.
Alice
A
Wang
Vi Doan, Pharm.D., is Postgraduate Year 2 Oncology Pharmacy Resident; Alice Wang, Pharm.D., BCOP, is Clinical Pharmacy Specialist; and Hillary Prescott, Pharm.D., BCOP, is Clinical Pharmacy Specialist, University of Texas MD Anderson Cancer Center, Houston.
Hillary
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Prescott
D000814:Aniline Compounds / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000473:pathology; D009570:Nitriles / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D011804:Quinolines / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*
D000814:Aniline Compounds; D000970:Antineoplastic Agents; D009570:Nitriles; D047428:Protein Kinase Inhibitors; D011804:Quinolines; C471992:bosutinib