Imatinib and norimatinib

Imatinib is now first-line treatment for chronic phase chronic myeloid leukaemia (CML). Imatinib has also proved successful in treating gastrointestinal stromal tumours (GIST). N-Desmethylimatinib (norimatinib) is the principal plasma metabolite of imatinib and accumulates to concentrations of approximately 20 % of those of imatinib during chronic therapy. It may possess pharmacological activity. Treatment failure has been attributed to poor adherence, inadequate dosage, or development of a mutation causing imatinib resistance. Thus, monitoring plasma imatinib and norimatinib may help in assessing adherence and in optimising treatment. Cytogenetic and molecular responses to imatinib have been associated with pre-dose plasma imatinib concentrations of 1 mg/L or more. In GIST a threshold for response of 1.1 mg/L has been suggested.