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Cytarabine Can Be Added Safely to Imatinib

Cytarabine Can Be Added Safely to Imatinib

ORLANDO—Low-dose cytarabine can be safely administered in
combination with imatinib mesylate (Gleevec, also known as STI-571) to chronic
myelogenous leukemia (CML) patients in blast crisis, but is unlikely to provide
substantial benefit or salvage relapses.

For patients in the chronic phase, the drug combination produces results
similar to those observed in phase I trials with imatinib alone. These findings
were presented by Brian Druker, MD, of Oregon Health & Science University,
Portland, at the 43rd Annual Meeting of the American Society of Hematology (ASH
abstract 3511).

The phase I trial followed in vitro studies showing synergistic
antiproliferative effects when cytarabine was used with imatinib in CML cell
lines and colony-forming assays of CML patient samples. As part of the phase I
study, 62 CML patients were treated with a combination of imatinib plus
low-dose cytarabine.

Blast Crisis

Patients in myeloid or lymphoid blast crisis (n = 28), plus four patients
with Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL), were
treated with escalating doses of 400, 600, or 1,000 mg of imatinib daily, with
cytarabine at a fixed dose of 20 mg/m² on days 15 through 28 of each cycle.
Response rates, durability of response, and toxicities were similar to those
reported in phase I studies of imatinib alone.

A total of 11 patients (34%) went on to receive stem cell transplants, Dr.
Druker reported. "So it is our conclusion that you can certainly use
imatinib plus cytarabine in a preparative regimen for patients prior to
transplant, but other combinations need to be considered for patients not
eligible for transplant."

Another cohort of eight patients in myeloid blast crisis who relapsed while
on imatinib continued on treatment with imatinib daily, and cytarabine was
added at 20 mg/m² on days 1 to 14. All of these patients later discontinued
treatment due to disease progression.


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