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LOS ANGELES, April 17 -- Darbepoetin alfa (Aranesp) should not be used for treatment of anemia caused by cancer, researchers here reported.

Compared with 432 placebo patients, 419 patients treated with darbepoetin had a significant decrease in the need for transfusion, but there was a 23% increase in the risk of death (P=0.031), said John Glaspy, M.D., of the University of California Los Angeles. Action Points

Explain to interested patients that this finding supports recent actions by FDA, which added boxed warnings to the labels of darbepoetin and similar products.

Explain to patients that this study did not include patients who developed anemia as a result of cancer treatments, only patients who had anemia as a result of their cancer.

This study was published as an abstract and presented orally at a conference. These data and conclusions should be considered to be preliminary as they have not yet been reviewed and published in a peer-reviewed publication.

On the basis of these findings, Dr. Glaspy said the "evidence does not support the use of erythropoietin in these patients." He reported results of the randomized trial at a late breaking clinical trials session at the American Association for Cancer Research meeting.

He noted, however, that the study did not address the use of darbepoetin and other anti-anemia agents for treatment of anemia due to chemotherapy. "That really represents the more common use of darbepoetin for cancer patients," he said.

Results from a trial of darbepoetin in cancer patients with anemia caused by chemotherapy are expected to be reported later this month.

Dr. Glaspy said it was unclear why treatment with erythropoietin products would increase mortality in cancer patients, but he said a number of theories including the possibility that "there may be EPO receptors on the cancer cells themselves" are being investigated.

Hematologist David P. Steensma, M.D., of the Mayo Clinic in Rochester, Minn., who was the discussant for the paper, said that reducing the need for transfusion is an important goal because transfusions are associated with a worse outcome in other settings, including studies of patients treated in intensive care units.

"And transfusions are not, themselves, without risk," he added noting that risks include "infection through the units transfused, prions, for example, are now a concern as well as the potential for febrile reaction, volume overload, or iron overload."

On March 9 the FDA ordered a black-box warning for all erythropoeisis-stimulating agents. The new label states that using the agents to raise hemoglobin to a target of 12 g/dL or higher were associated with "serious and life-threatening side-effects and/or death."

Moreover, the FDA said then that for cancer patients who are not on chemotherapy, the agents -- including darbepoetin -- did not benefit anemia. But they appeared to shorten time to death.

The current study randomized 985 patients to darbepoetin at 6.75 mcg/kg or placebo every four weeks for 16 weeks. There was an end of study assessment at 19 weeks and patients were followed for two years to evaluate survival.

Inclusion criteria included hemoglobin of 11 g/dL or less as wells as no chemotherapy or radiation therapy within four seeks of screening for the study.

The primary endpoint was occurrence of transfusion from week five to week 17. The secondary endpoints were occurrence of transfusion from week five to week 17, change in hemoglobin from baseline to week 17, and safety.

The mean age of 851 patients was 64 and the most common cancers were non-small cell lung cancer, breast, and prostate cancer. Most patients had stage III or IV disease and 72% had an ECOG score of 0 or 1 at baseline. Average baseline hemoglobin was 9.5 g/dL.

Although the groups were generally well balanced, 55% of the 419-patient darbepoetin group was men versus 47% of the 432-patient placebo group and more patients in the darbepoetin group had received previous chemotherapy.

Among the findings:

There were 176 transfusions in the darbepoetin group versus 215 in the placebo group (P=0.320).

There were fewer red blood cell transfusions in the darbepoetin group and when this was stratified by hemoglobin of 8 g/dL or less, the difference was statistically significant (P=0.022).

There were 216 deaths in the placebo arm and 250 in the darbepoetin arm (HR for time to all deaths darbepoetin versus placebo 1.23, (95% CI 1.02 to 1.48, P=0.031).

The study enrolled patients in the United States and Europe. Dr. Glaspy said it was limited by differences in transfusion patterns in some eastern European countries. "The problem was that blood products for transfusion were not always available at some eastern European centers," a difficulty that he said was probably not "an ideal situation for a trial that has transfusion rate as its primary endpoint."

The trial was funded by Amgen. Drs. Glaspy and Steensma declared no relevant conflicts.

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