Results from a large, randomized clinical trial (E1900) of 657 patients between the ages of 17 to 60 with previously untreated acute myeloid leukemia (AML) demonstrated that patients who received a high dose of a commercially available chemotherapy drug, daunorubicin, during initial therapy lived longer than patients who received a standard dose of the same drug. Daunorubicin, a drug originally approved for use by the U.S. Food and Drug Administration in 1979, inhibits DNA replication and repair and leads to cell death. This clinical trial was sponsored by the NCI and conducted by a network of researchers led by the Eastern Cooperative Oncology Group (ECOG).
Researchers found that the patients in the trial who received the higher dose of daunorubicin (90mg/m²), given on each of the first three days of treatment in combination with cytarabine, had a higher complete remission rate (70.6 percent) and improved median overall survival (23.7 months) compared to patients treated with standard dose daunorubicin (45 mg/m²), given in combination with cytarabine, who had a complete remission rate of 57.3 percent and median overall survival of 15.1 months. The differences in complete remission rates and overall survival were highly statistically significant. Also of importance, the frequency of serious treatment toxicities observed in this study was similar between the high-dose and standard-dose daunorubicin treatment groups. Median follow-up for patients in the study was 25.2 months.
Fernandez HF, Sun Z, Yao X, et al. Anthracycline dose intensification in acute myeloid leukemia. N Engl J Med 2009:361;1249-59. http://www.ncbi.nlm.nih.gov/pubmed/19776406