Stronger Doses for Some Leukemias

Acute myeloid leukemia genetic variations and adjusted daunorubicin dosages

(RxWiki News) Established guidelines form the baseline for cancer treatment, and oncologists tailor the standard therapy based on individual response. Movement to personalized treatment based on genetic variations instead looks to be the future of cancer therapy.

Researchers from Case Western Reserve University School of Medicine have identified genetic mutations that benefit from higher doses of chemotherapy in patients with acute myeloid leukemia (AML).

Their study found that in cancers with these mutations, a single megadose of chemotherapy improved overall outcomes compared to spacing out several cycles.

"Ask your oncologist about their use of genetic profiling to treat cancer."

In a study of 398 patients, eighteen genes were analyzed for mutations, and patients were assigned to a standard or high dose regimen of the chemotherapy drug daunorubicin. Results from that study were used to construct a new, independent study in 104 different patients to validate the findings.

Patients with mutations or gene shifts in cancer genes DNMT3A, NPM1, or MLL, were shown to benefit from the high dose daunorubicin chemotherapy, improving both survival and remission rates.

"This is yet another advance in the era of 'individualizing' a patient's care," study author Hillard Lazarus M.D. said. "These significant findings will provide an important new tool to predict patients' response to cancer-fighting therapies and will help physicians avoid over-treating some patients and under-treating others."

"Information of this type could be used by a clinician for treatment planning at diagnosis and the start of therapy," said Dr. Lazarus. "That is, if the patient has the mutation in question, the clinician can go ahead and give the higher chemotherapy dose. If the patient does not have the mutation, a higher dose may not be of benefit."

The study was published in the New England Journal of Medicine, building on an initial study in 2009 published in the same journal that demonstrated for the first time that a more intense initial regimen using higher doses of daunorubicin significantly improved remission rate (70.6% vs. 57.3% with a standard dose) and improved overall survival (median, 23.7 vs. 15.7 months). More patients achieved remission with only one cycle of therapy, rather than two cycles, more patients proceeded to transplant, and overall outcome was significantly improved.

Dr. Lazarus said, "These findings show how genetic information can be used to 'tailor' therapy for patients. Now the challenge before us is to find a way to provide this genetic information in a timely and affordable way to influence treatment decisions for patients. Hopefully we can answer additional important questions such as these by continuing to enroll patients onto clinical trials."

The research was funded by a mixture of public grants from the National Cancer Institute as well as private funds from non-profit and academic organizations.

Review Date: 
March 23, 2012