Administering cytarabine at levels
substantially higher than the standard dose can cure nearly five
times as many patients who have a certain type of acute myeloid
leukemia (AML), according to a recent study.
The study, which appeared in the September issue of Cancer Research,
revealed that 78% of patients with core binding factor
AML who received high-dose cytarabine were in complete remission 5
years after treatment (and therefore potentially cured), as compared
with only 16% of those who received the standard dose.
It is truly remarkable to achieve a cure rate of over 75% in a
subgroup of adult leukemia patients; this rate approaches that for
some types of childhood leukemia, said Clara Bloomfield, lead
author of the study, director of Ohio State Universitys
Comprehensive Cancer Center, and William G. Pace III Professor of
Cancer Research. Because high-dose cytarabine is quite toxic,
especially for older people, we want to use it only with those
patients who will benefit. These results tell us which patients we
can cure, and which ones should receive other therapy.
The finding is considered particularly strong because the study
followed patients for more than 7 years after treatment; most such
studies rely on models to project estimates of 5-year remission rates.
The study involved 285 newly diagnosed AML patients age 16 years and
older who were in remission. During the intensification phase of
their treatment, the patients were randomly assigned to receive
cytarabine at either standard dose (100 mg/m²), intermediate
dose (400 mg/m²), or high dose (3,000 mg/m²).
Patients Stratified by Chromosomal Abnormalities
These groups of patients were then subdivided into three categories
according to their cytogenetics. Patients showing damage to
chromosome 16 or to chromosomes 8 and 21 were assigned to the
core binding factor (CBF) group; those with no visible
chromosome damage were assigned to the normal group; and
those with other types of chromosome damage were assigned to the
other abnormalities group.The outcome of the patients in
each chromosome group and at each dose was then examined.
Of the 57 patients in the CBF group, 78% of those who received the
high drug dose were in complete remission, as opposed to only 57% of
those who received the intermediate dose and 16% of those who
received the standard dose.
Of the 140 patients in the normal group, 40% of those who
received the high drug dose were in complete remission, as compared
with 37% of those who received the intermediate dose and 20% of those
who received the standard dose.
Finally, of the 88 patients in the other abnormalities
group, complete remissions were noted in 21% of those who received
the high dose, 13% of those who received the intermediate dose, and
13% of those given the standard dose.
In the other abnormalities group, the dose of
cytarabine made no difference, said Dr. Bloomfield. But
in the normal group, using high-dose cytarabine doubled the number of
patients cured, and in the CBF group, the high-dose treatment
increased the number by nearly five times. Because of these results
and this astronomical difference, we now routinely treat CBF patients
using high-dose cytarabine.
Implications for Future Research
The ramifications of these findings are tremendous. A lot
of people are now working to understand why patients with core
binding factor leukemias are particularly sensitive to this drug, and
that may help us design more rational treatments in general. Its
an excellent example of how clinical findings can spur new
laboratory research and perhaps improve cancer treatment in the future.