bosutinib

Bosutinib is an oral small-molecule anticancer drug classified as a tyrosine kinase inhibitor. It targets BCR-ABL, the fusion protein driving Philadelphia chromosome–positive chronic myeloid leukemia (CML), and also inhibits Src family kinases. By blocking these kinases, bosutinib interferes with signaling pathways that promote leukemic cell growth and survival.

Mechanism of action: Bosutinib binds to the ATP-binding site of BCR-ABL and Src kinases, inhibiting their phosphorylation activity. This dual inhibition disrupts signaling necessary for leukemic cell proliferation and can lead to reduced disease activity in patients with CML.

Medical uses: In many regions, bosutinib is approved for adult patients with chronic-phase CML who have resistance or intolerance to prior tyrosine kinase inhibitor therapy. It is not commonly used as first-line therapy, although clinical studies have explored such use. It has been investigated in other BCR-ABL–driven leukemias and in various solid tumors, but its approved indication remains primarily CML in this context.

Administration and dosing: Bosutinib is taken orally, typically as 500 mg once daily with a meal. Dosing may be adjusted based on tolerance, liver function, and potential drug interactions. Patients should be monitored regularly for adverse effects and liver enzyme elevations.

Pharmacokinetics: Bosutinib is extensively metabolized in the liver, mainly by CYP3A4. Drug exposure is increased by strong CYP3A inhibitors and decreased by CYP3A inducers. The elimination half-life is in the vicinity of a day, with the drug primarily cleared hepatically and to a lesser extent renally.

Adverse effects: The most common side effects are diarrhea, nausea, vomiting, abdominal pain, and skin rash. Hepatic enzyme elevations (ALT/AST), thrombocytopenia, and neutropenia can occur, along with fatigue and edema. Serious liver injury is a potential risk requiring monitoring.

History: Bosutinib (brand name Bosulif) was developed by Wyeth and later marketed by Pfizer. It received regulatory approval in 2012 for CML patients with resistance or intolerance to prior therapy.