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When Less Is More: Smaller Doses Of Chemo May Be Equally Effective In AML

A recent issue of the New England Journal of Medicine includes an article with the bland title Cytarabine Dose for Acute Myeloid Leukemia. AML is an often-curable form of leukemia characterized by rapidly-growing myeloid white blood cells. Cytarabine — what we’d call “Ara-C” on rounds  — has been a mainstay of AML treatment for decades.

The new report* covers a fairly large, multicenter, randomized trial of adult patients with AML. The researchers, based in the Netherlands, Switzerland, Belgium and Germany, evaluated 860 patients who received either intermediate or high doses of Ara-C in their initial, induction chemotherapy. According to the journal, “this investigator-sponsored study did not involve any pharmaceutical companies.”

The main finding was that at a median follow-up of 5 years there were no significant differences between the groups in terms of complete remission rates, relapses or overall survival. The high-dose Ara-C offered no clear advantage in any prognostic subgroup, including those with genetic changes that bear a poor risk. Not surprisingly, Grade 3 and 4 (severe) toxicities were more common in the patients who received higher doses of Ara-C. Those patients also had lengthier hospitalizations and prolonged reduction in their blood counts.

Why am I mentioning this report, besides that it hasn’t received any press coverage? First, because the findings might matter to people who have AML and are contemplating treatment options. But mainly it’s an example of how carefully dialing down some chemotherapy doses could reduce health care costs and lessen untoward effects of cancer therapy — in terms of early toxicities and, possibly down the line, fewer secondary malignancies – without compromising long-term outcomes.

*subscription required: N Engl J Med 364: 1027–36 (2011). The free abstract includes some details on the chemo doses.

*This blog post was originally published at Medical Lessons*


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