HEALTH-SYSTEM EDITION
CLINICAL PRACTICE

Less frequent dosing makes difference between two EPOs

The latest comparison study of darbepoetin alfa (Aranesp, Amgen) versus epoetin alfa (Procrit, OrthoBiotech) provides further evidence that darbepoetin alfa dosed every two weeks is as safe and effective as weekly epoetin alfa in correcting chemotherapy-induced anemia, according to a report presented at the annual meeting of the American Society for Clinical Oncologists (ASCO), held recently in Chicago.

"Darbepoetin alfa given at a dose of 3.0 mcg/kg every two weeks safely raises hemoglobin concentration to the same extent as epoetin alfa at the standard equivalent dose of either 40,000 U once or 150 U/kg three times weekly," said lead researcher Barry Mirtsching, M.D., an oncologist in private practice and a clinical investigator from the Center for Oncology Research & Treatment in Dallas.

While the two molecules are similar in structure, Mirtsching said, the new agent has two more glycosylation sites than epoetin, giving darbepoetin a three-fold longer half-life that makes possible a longer interval between doses. "This study is not the long-awaited head-to-head clinical trial directly comparing the two agents," he noted. "That large randomized trial is under way." But in the meantime, "this in-depth comparison of well-established published data on hemoglobin response after treatment can help clinicians and pharmacists understand which compound to use now for the patient with cancer-related anemia."

Mirtsching's report at ASCO is an evaluation of pooled data from three multicenter trials of similar design conducted in the United States, including interim data from one recently completed 1,167-patient study. Analyzed were 402 anemic patients receiving multicycle chemotherapy for many types of common tumors, such as breast, lung, gynecologic, and lymphoma. They received subcutaneous injections of the open-label study drug—either darbepoetin or epoetin alfa.

Mirtsching explained that 260 of these patients received darbepoetin at 3.0 mcg/kg every two weeks, with a dose escalation to 4.5 mcg/kg in week seven allowing for an inadequate hemoglobin response. Another 115 patients received epoetin at 40,000 units weekly or 150 U/kg three times a week with dose escalations at four weeks to 60,000 U weekly or 20,000 U three times a week, also allowed by study design.

The researchers focused on hematopoietic response (i.e., a hemoglobin increase of 2 gm/dl or increase in hemoglobin to 12.0 gm/dl) after four and 12 weeks of treatment, as well as frequency of transfusion and standard safety parameters. They found:

Patients on either drug had a similar favorable reaction to treatment—i.e., 79% of 287 patients receiving darbepoetin every two weeks and 71% of 115 receiving epoetin once or three times a week had an optimum hematopoietic response. "This, in turn, produced relief of anemia-related symptoms as well as a good quality of life," said Mirtsching. Here are some other findings:

• The proportion of patients requiring transfusions was virtually identical in both groups at week five to the end of treatment—15% for darbepoetin versus 14% for epoetin.

• The safety profiles of both drugs were similar. "Few serious events, no unmanageable rapid increases in hemoglobin, and no confirmed neutralizing antibodies were reported in the combined three studies we evaluated," he said.

Mirtsching concluded, "The therapeutic impact of darbepoetin alfa 3.0 mcg/kg administered every two weeks to treat chemotherapy-induced anemia was comparable to that seen with epoetin alfa but occurred with less frequent dosing."

Naomi Pfeiffer

The AUTHOR is a clinical writer based in New York.

Naomi PFEIFFER. Less frequent dosing makes difference between two EPOs.

Drug Topics

Jul. 21, 2003;147:HSE21.