NEW YORK-Weekly injections of epoetin alfa (Procrit) might protect breast cancer patients against anemia and improve their quality of life during adjuvant chemotherapy.
NEW YORKWeekly injections of epoetin alfa (Procrit) might protect breast cancer patients against anemia and improve their quality of life during adjuvant chemotherapy.
Interim results from the first 852 women in a large multicenter study show significant gains in energy and activity as well as in hemoglobin levels compared to historic data on women who did not receive erythropoietic therapy during adjuvant chemotherapy (ASCO abstract 1518). Up to 1,700 women with mid-range hemoglobin levels are to be enrolled in the ongoing phase IV study, and a randomized trial is contemplated, according to lead investigator Clifford A. Hudis, MD, chief of the Breast Cancer Medicine Service at Memorial Sloan-Kettering Cancer Center in New York City.
"The bottom line, we think, is that this suggests the possibility that weekly epoetin alfa will maintain hemoglobin in adjuvant therapy patients," Dr. Hudis told ONI. ‘‘It will protect against anemia. We are being very conservative; it will moderate decreases in quality of life. In fact it looks like [the patients] get a little bit better. And we need a prospective randomized trial to ever be definitive about these things."
Expansion in Thinking
The investigation represents an expansion in thinking about what erythropoietic therapy can do for patients, according to Dr. Hudis. In the early 1990s, research focused on improving hemoglobin levels in anemic patients and on avoiding transfusions, but it was directed mostly at patients near the end of life, he said.
Later studies began to look at the impact on quality of life, but still in the sickest patients. Only recently have investigations begun to look at whether erythropoietic therapy can have a positive impact on healthier patients and perhaps protect cognitive functioning during chemotherapy.
"These are potent biological agents, and they may have an effect beyond simply inducing red cell count," Dr. Hudis said.
The women in the adjuvant breast cancer study do not have major medical problems beyond early-stage (I-III) breast cancer, and their hemoglobin levels are in the 10 g/dL to 14 g/dL range when they enter the study. Dr. Hudis describes the qualifying counts as "that midrange where healthy people are when they are being treated for cancer, but before you are thinking a lot about anemia."
While receiving an anthracycline with or without a taxane as adjuvant therapy, the participants are given erythropoietic therapy starting at 40,000 units of epoetin alfa weekly for up to 24 weeks as well as daily supplemental iron. If hemoglobin does not increase by more than 1 g/dL for a woman starting in the 10 g/dL to 12 g/dL range or decreases more than 2 g/dL in a woman at the higher range, the patient is raised to 60,000 units. Therapy is stopped if a patient’s hemoglobin count goes above 15 g/dL.
The last recorded data showed the mean final hemoglobin was 13.2 g/dL, an increase of 0.9 from baseline. "We’re driving people to pretty high hemoglobin levels, especially when undergoing treatment for cancer," Dr. Hudis said, citing historic comparisons. "What we see is in this cohort of patients is that hemoglobin went up during [chemo]therapy. You would have expected hemoglobin to fall."
Not only was epoetin alfa well tolerated, but patients also showed an improvement in quality of life based on the Linear Analog Scale Assessment (LASA) and the Functional Assessment in Cancer Therapy-Anemia Scale (FACT-An). The investigators reported that weekly epoetin alfa therapy had raised overall quality of life from a mean baseline value of 66.5 to 69.2 on the LASA scale. Significant improvements were seen in energy, which went from a mean score of 59.9 to 64.3, and in activity, which went from 62.1 to 66.3. "The median patient reported a rise in quality-of-life parameters," Dr. Hudis said.
Despite the challenges in quantifying quality-of-life improvements, Dr. Hudis said he thought improving quality of life was important to cancer patients. Noting that many patients will not be cured, he said, "If I had my choices of things in life, I’d rather feel better, even if I don’t do better, and if I do better, that’s a bonus." He declined to discuss cost issues, but suggested the cost could be justified if people feel well enough to work during cancer therapy and are more productive, contributing to society.
Only a large, head-to-head trial could make meaningful comparisons between epoetic alfa and darbepoetin alfa (Aranesp), a newer erythropoietic therapy agent, Dr. Hudis noted. On the one hand, he said, darbepoetin alfa’s longer serum half-life is a potential advantage because being able to give the new agent less often could have a significant impact on quality of life. On the other hand, he continued, peak dose and efficacy are also important considerations.
"For a theoretical drug, it could be you get your benefit when you have a threshold that is crossed, and the duration of exposure may not be as important for some drugs," he said. "The truth is, the bottom line is not the half-life for the drug. The bottom line is the clinical efficacy."