Physical Address
304 North Cardinal St.
Dorchester Center, MA 02124
Lapatinib
General information
Tyrosine kinase inhibitors are effective in the targeted treatment of various malignancies. Imatinib was the first to be introduced into clinical oncology, and it was followed by drugs such as gefitinib, erlotinib, sorafenib, sunitinib, and dasatinib. Although they share the same mechanism of action, namely competitive ATP inhibition at the catalytic binding site of tyrosine kinase, they differ from each other in the spectrum of targeted kinases, their pharmacokinetics, and their adverse effects and reactions [ ].
Lapatinib, a 4-anilinoquinazoline derivative, was the first dual tyrosine kinase inhibitor. In contrast to erlotinib and gefitinib, it inhibits both the ErbB1/HER1 (EGFR) tyrosine kinase and the ErbB2/HER2 tyrosine kinase simultaneously. It is used in patients with advanced metastatic breast cancer who are refractory to anthracyclines or taxanes together with trastuzumab [ ]. It is given orally in a dose of 1.25 g/day on days 1–14 every 21 days together with capecitabine (1.0 g/m 2 bd on days 1–14 every 21 days).
Grade 3 diarrhea is dose-limiting, whereas adverse reactions such as acneiform rash, nausea, and fatigue are moderate (grades 1–2).
Pharmacokinetics
Lapatinib peak concentrations are reached after 3–4 hours [ ]. Absorption is increased about three-fold when it is given with a meal, and administration on an empty stomach has been recommended, in contrast to the co-administered capecitabine, which should be taken with food. The half-life of lapatinib increases significantly from about 11 hours to 24 hours during repeated administration, probably because of inhibition of CYP3A4. Lapatinib crosses the blood–brain barrier, which may help in the treatment of brain metastases, which are of concern in about one-third of women with ErbB2 over-expression. Elimination is primarily by hepatic metabolism and biliary excretion; renal excretion is minor. Recovery of lapatinib in the feces accounts for about 27% (3–67%) of an oral dose.
You're Reading a Preview
Become a Clinical Tree membership for Full access and enjoy Unlimited articles
If you are a member. Log in here