Administering cytarabine(Drug information on 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.