More Convenient Dosing for Erythropoietin in Cancer Fatigue Patients

NEW ORLEANS—A less frequent dosing schedule of recombinant human erythropoietin (epoetin alfa, Epogen, Procrit) may offer effective and more convenient treatment for the fatigue and malaise associated with cancer therapies, said George D. Demetri, MD, medical director, Center for Sarcoma and Bone Oncology, Dana-Farber Cancer Institute.

Speaking at a satellite symposium preceding the 41st Annual Meeting of the American Society of Hematology (ASH), Dr. Demetri pointed out that the commonplace three-times-weekly erythropoietin dosing strategy is derived from the typical schedule for dialysis patients, not from research into optimal dosing. Equivalent efficacy can be achieved, he said, with once-weekly dosing, provided that higher doses are used.

Considering what has been learned about the use of epoetin alfa in the renal dialysis setting, not enough is being done for cancer patients, Dr. Demetri suggested. Beyond avoiding transfusions, end-stage renal disease patients have demonstrated improvements in quality of life, exercise tolerance, and physical and cognitive function with epoetin alfa.

While use of epoetin alfa has become “a reasonable thing to think about” for cancer patients, treatment for anemia has been too often ignored in the past or delayed until transfusion of red cells was required, he said.

Randomized controlled trials of epoetin alfa conducted 10 years ago among cancer patients receiving or not receiving chemotherapy showed anemia responding in all groups. Other studies have shown that mean weekly hematocrits in chemotherapy patients diverge sharply with use of epoetin alfa, compared with placebo, as soon as 2 weeks after the inception of therapy.

Dr. Demetri’s own study (J Clin Oncol 16:3412-3425, 1998) among more than 2,000 patients demonstrated a direct correlation between increasing hemoglobin levels and improved energy, activity, and overall quality of life. Analysis of an even larger database covering more than 4,500 cancer patients further confirms these benefits, Dr. Demetri said.

“Patients are telling us, with remarkable consistency, that as hemoglobin levels improve, they somehow feel better and are functioning better,” he commented. He noted, however, that oncology patients require higher doses than renal failure patients, and that more than half do not respond. “We need to find out which patients have the most benefit,” Dr. Demetri added.

NESP Promising

NESP (novel erythropoiesis stimulating protein) is an investigational molecule rationally designed as a hyperglycol-sylated substance with delayed clearance. Phase III studies of the new agent are promising, Dr. Demetri said. Trials in 522 dialysis patients have shown that once-weekly or even biweekly NESP dosing increases hemoglobin levels similarly to epoetin alfa dosed once weekly to three times weekly. “The half-life of NESP given intravenously or subcutaneously is two- to threefold longer than conventional epoetin alfa,” he said.

No antibodies against NESP or endogenous human erythropoietin have been detected in patients receiving NESP, he said. Ongoing research aims to identify the least intrusive dosing schedule that will yield clinically significant efficacy.

Dr. Demetri pointed out other important research questions concerning fatigue management: Can we stimulate erythropoiesis in patients refractory to epoetin alfa or NESP? Beyond stimulation of erythropoiesis, can other mediators of fatigue and malaise be reversed, leading to more comprehensive fatigue management in cancer patients?

He urged further study aimed at determining whether improved functional status in fatigued cancer patients leads to economic benefits from either return to employment or reductions in health care costs.

Dr. Demetri commented, “Patients are very willing to pay for alternative medicines that don’t have the biology and research behind them that erythropoiesis has. But nothing is more natural than stimulating erythropoiesis with your own normal hormonal processes.”