Cancer treatment with bosutinib

Chronic Myelogenous Leukemia (CML) occurs mainly in patients with an abnormal chromosome called the Philadelphia chromosome. The abnormal chromosome causes production of Bcr-Abl protein. This protein is a tyrosine kinase, an enzyme which acts in the bone marrow, where blood cells are made. It causes too many white blood cells to be produced, as well as immature stem cells called blasts. These replace other important cells made in bone marrow, including platelets and red blood cells.

There are other tyrosine kinases. Tyrosine kinases in general regulate protein behavior inside cells by attaching phosphate groups to small molecules or proteins. In the presence of the abnormal Bcr-Abl protein, Abl kinase is unregulated. There are a number of drugs that inhibit tyrosine kinases. What is needed to treat CML is an inhibitor that works mainly on the Bcr-Abl mutation and not on tyrosine kinases needed for normal cells.

Many tyrosine kinase inhibitors have been found and used to treat both CML and ALL (acute lymphoid leukemia). The first of these is called imatinib and is now standard chemotherapy for Philadelphia chromosome positive CML. It is also used in conjunction with other drugs for some patients with ALL. Patients often become resistant to imatinib. Over-expression of specific Src kinases is associated with imatinib-resistant cases of CML. In resistant cases, one of the next generation of tyrosine kinase inhibitors, including nilotinib and dasatinib, might be used for treatment. Imatinib (trade name Gleevec) was FDA approved in 2001, dasatinib (trade name Sprycel) in 2006 and nilotinib (trade name Tasigna) in 2007.

Looking forward, an ongoing study in Florida, Georgia and Iowa is comparing bosutinib to imatinib in newly diagnosed, Philadelphia chromosome positive CML. Wyeth, which makes bosutinib, is the responsible party for the study. It is still recruiting patients, and is expected to run for eight years.

A second is a two-part safety and efficacy study of bosutinib, ongoing in the United States, Canada, Germany, the Netherlands, Italy and Spain. The first part of the study will be to determine the maximum tolerated dose of the drug. After that is completed, the second part will be to show that patients in all phases of Philadelphia positive CML and ALL will derive benefit from bosutinib at or below the maximum tolerated dose. This study is expected to last 5 years, and is still recruiting patients.

Anyone interested in more information about bosutinib or the ongoing studies can visit http://clinicaltrials.gov/ct2/home
There is a search engine to find studies of interest.

It seems very likely that bosutinib will receive FDA approval for CML treatment in the not-too-distant future.