ORLANDO, FloridaUpdated data from two phase II trials show that
imatinib mesylate (Gleevec, STI571) continues to improve response rates for
patients with chronic myelogenous leukemia (CML) who did not respond to
interferon therapy or are in blast crisis. With follow-up of 12 months or
more, overall and complete response rates are proving to be durable and
Imatinib inhibits the Philadelphia chromosome, a translocation between
chromosomes 9 and 22 that is detected in 95% of CML patients. The
Philadelphia chromosome produces Bcr-Abl, a tyrosine kinase that jams the
signal to halt production of white blood cells, thus allowing the massive
increase in the number of white blood cells that characterizes CML.
Imatinib is generally well tolerated. Although the majority of patients
treated with imatinib experience adverse events at some time, most events
are mild to moderate, as were those reported in the phase II studies. The
most common side effects included nausea, fluid retention, vomiting,
diarrhea, hemorrhage, muscle cramps, skin rash, fatigue, headaches,
dyspepsia, and dyspnea. Serious side effects include hepatotoxicity, fluid
retention syndrome, neutropenia, and thrombocytopenia.
In most countries where imatinib is approved, it is indicated for the
treatment of patients in chronic phase after failure with interferon,
accelerated phase CML, or blast crisis.
Failed Interferon Therapy
Updated follow-up on 532 patients who have late CML and failed interferon
therapy confirmed and expanded response and survival rates. The reasons for
interferon failure were hematologic resistance or refractory to interferon
(152), cytogenetic failure (188), and intolerance to interferon (192).
Treatment was imatinib at a dose of 400 mg/d. The median age was 57,
"similar to the age of an unselected CML population," noted Hagop
P. Kantarjian, MD, of The University of Texas M. D. Anderson Cancer Center
in Houston. "Currently, the median duration of treatment is 18 months,
and most of the patients (90%) have been treated for longer than 1
year," Dr. Kantarjian said.