For instance, in the ECOG study overall, complete remission rates jumped from 57.3 percent for the standard treatment group, to 70.6 percent for the high-dose group, while median survival improved from 15.7 months to 23.7. For those patients younger than 50, survival improved from a median of 19 months, to 34.3 months. But no benefit was seen for patients 50 or older.
Similarly, survival improved from 20.7 to 34.3 months for patients with "favorable" or "intermediate" genetic profiles, but no benefit at all was observed in patients with an "unfavorable" profile.
In the European trial, overall complete remission rates rose in the high-dose group from 54 percent to 64 percent, with no overall improvement in two-year overall survival. Yet when looking only at patients aged 60 to 65, remission improved from 51 percent to 73 percent, while two-year survival improved from 23 percent to 38 percent.
"I think the take-home message is that the outcomes seem to be sufficiently improved, at least in patients less than 50, and aged 60 and 65, that this is a reasonable standard of care," said Dr. Michael Millenson, director of the hematology service at the Fox Chase Cancer Center in Philadelphia. He added, "Since we don't necessarily have all the cytogenetic information back when we have to make a decision about dosing, I think the reassuring thing is that there didn't seem to be excessive toxic side effects."
Dr. Anthony Stein, of the City of Hope in Duarte, Calif., who sees "at least two new AML patients per week," uses idarubicin rather than daunorubicin. But, he said, "based on these two papers, it didn't look like using the higher dose led to more toxicity, so if I were going to use daunorubicin, I would use the higher dose."
Dr. Barton Kamen, chief medical officer at the Leukemia & Lymphoma Society, said the studies highlight the heterogeneity of AML and the power of "personalized medicine" -- as well as the need for more research.
"To me the tagline is, AML is lots of different diseases," Kamen said. "And we need to know as much as we can of the patient and the disease to treat them. This is a spectacular example of that."
"But," he added, "they still have a lot of work to do."
Kamen doesn't advocate giving high-dose daunorubicin to all patients, only those who are likely to benefit. "There are short- and long-term side effects we don't know yet," he said. Of particular concern, daunorubicin can damage the heart.
Indeed, Fernandez noted there are "nay-sayers" in the oncology community who suggest that, five or six years down the road, patients might be better off had they received the lower dose. "But my retort is, with the high dose, they are more likely to be alive."
For more information on AML, visit the Leukemia & Lymphoma Society.
SOURCES: Hugo F. Fernandez, M.D., associate member and associate chair, department of blood and marrow transplantation, Moffitt Cancer Center and Research Institute, Tampa, Fla.; Anthony S. Stein, M.D., professor, hematology and hematopoietic cell transplantation, associate member, hematologic malignancies program, Comprehensive Cancer Center, City of Hope, Duarte, Calif.; Barton A. Kamen, M.D., Ph.D., chief medical officer, Leukemia & Lymphoma Society; Michael Millenson, M.D., director, Hematology Service, Fox Chase Cancer Center, Philadelphia; Sept. 24, 2009, New England Journal of Medicine