Background: The drug Gleevec (imatinib) is now widely used in treating CML (chronic myeloid leukemia). It is also approved worldwide for treating gastrointestinal stromal tumors (GIST). But in the case of GIST, it is not known if a dose of Gleevec that is higher than recommended is better or worse.
Summary: A clinical trial was done involving 946 patients with GIST. The patients were randomly assigned to receive 400 mg of Gleevec either once or twice a day. The dose of 400 mg of Gleevec twice a day was found to achieve significantly longer survival without progression of the tumor.
Personal Comment: Thirty years ago one of us lost his brother Mac to CML. Mac's leukemic cells had the characteristic Philadelphia (Ph) chromosome, a product of a translocation between chromosomes 9 and 22. That's all we knew at the time of Mac's death. We now know much more. We know that the translocation in Mac's leukemia cells had fused the ABL oncogene with the BCR gene. We know that this resulted in the production of an abnormal protein. We know that this process caused his malignancy. Understanding this process has led to the development of Gleevec, the first genetically targeted drug for cancer treatment.
