About this kinase inhibitor, Nilotinib

Chemists created nilotinib with the idea of improving the target specificity of an earlier kinase inhibitor, imatinib. Studies show it is 20 to 50 times stronger than imatinib. Nilotinib is also intended to be specific for BCR-ABL.

The manufacturer, Novartis, says Nilotinib caused a hematologic response in 74% of cases in clinical trials for use on Ph+ CML leukemia. CML makes up 15% of leukemia cases in adults, and the Philadelphia chromosome (the Ph+ designation) is present in most CML patients.

This agent also inhibits the receptor tyrosine kinases platelet-derived growth factor receptor (PDGF-R) and c-kit, a receptor tyrosine kinase mutated and constitutively activated in most gastrointestinal stromal tumors (GISTs).

The dosage of nilotinib directly affects the patients' T-cell count in the blood. A German study found that the dose needed to be higher than the normal clinical dose to control cytokine production.

As scientists learn more about kinase inhibitors as a class of drug, it appears that these drugs seem to improve the action of cancer treatment in certain conditions, but actually have detrimental effects in other conditions. For clinical evaluation purposes, these conditions are going to most often be the presence of other chemotherapy agents.

In October 2007, the FDA approved Nilotinib for CML. Specifically, the medicine was approved for the chronic phase and accelerated phase Philadelphia chromosome positive (Ph+) chronic myelogenous leukemia. Doctors have the authority to prescribe the medicine for other conditions, and it may happen that nilotinib is combined with other medicines for treatment. The approval process for nilotinib was faster than for most anti-cancer drugs, partly because of its similarity to imatinib.

In June 2008 Italian doctors presented evidence of the efficacy and tolerability of nilotinib in CLL. The complete cytogenic response among patients in their tests was 84%.