Treating Mild Anemia Reduces Fatigue, Clinic Visits

PHILADELPHIA—Chemotherapy patients whose hemoglobin (Hb) drops below 9 g/dL are typically treated with recombinant human erythropoietin, but those whose anemia is in the 10 to 12 g/dL range are typically not given hematopoietic support.

Interim data from a study presented at the 44th Annual Meeting of the American Society of Hematology (ASH abstract 828) suggest that boosting hemoglobin above this mild-to-moderate range not only reduces fatigue but also reduces the number of clinic visits and the number of days of missed work.

"Current guidelines from both ASH and the American Society of Clinical Oncology recommend treating anemia in chemotherapy patients whose hemoglobin drops below 10 g/dL, but state that treatment for patients whose levels are between 10 g/dL and 12 g/dL is optional and at the discretion of the physician. About 30% of these moderately anemic chemotherapy patients are getting epo-etin alfa. Our question was how much this benefited patients in terms of quality of life and cost, as well as in correction of anemia," lead investigator David J. Straus, MD, of the Lymphoma Service, Memorial Sloan-Kettering Cancer Center, told ONI in an interview.

The trial, sponsored by Ortho Biotech, closed on August 31, 2002, with 265 patients evaluable. Dr. Straus reported interim data on 179 patients.

This study was a randomized, open-label, multicenter, 16-week trial that assessed the effect of once-weekly epoetin alfa (Procrit) in patients with lymphoma, chronic lymphocytic leukemia (CLL), or multiple myeloma who were receiving chemotherapy and who had mild-to-moderate anemia (baseline Hb 10 to 12 g/dL).

Patients were enrolled in this trial at the beginning of their chemotherapy and randomized to epoetin alfa or observation, with the observation group to receive epoetin alfa only if their Hb dropped below 9 g/dL. "Patients were treated with epoetin alfa according to current guidelines if their prechemotherapy Hb levels were between 10 g/dL and 12 g/dL, and those with Hb levels above 12 g/dL were not eligible for randomization unless their levels fell below 12 g/dL while on chemotherapy," Dr. Straus said.

Hemoglobin, disease status, quality of life (QOL), and health care resource use were assessed monthly. Quality of life was measured by the Functional Assessment of Cancer Therapy-Anemia (FACT-An) and by the Linear Analog Scale Assessment (LASA). The Health Resource Utilization Scale was used to estimate use of health care resources, but this has not yet been tied to dollar estimates.

In total, 77 patients were randomized to receive weekly epoetin alfa (40,000 U subcutaneously) and 102 to observation. Dr. Straus said that most patients received epoetin alfa at home and that some (particularly younger patients) successfully learned to self-administer the drug. The cost of epoetin alfa at the dose used in this study is about $540 per week.

Dr. Straus said that data available for the interim analysis did not permit statistically valid comparisons between treatment and control groups, apart from the health resources utilization analysis.

Study Results

"The preliminary within-group analysis shows clearly that treatment with epoetin alfa improved both hemoglobin levels and quality of life, compared to baseline," Dr. Straus said.

Hemoglobin levels in epoetin alfa-treated patients increased from 11.3 g/dL at baseline to 12.9 g/dL (P = .005) but remained relatively unchanged at 11.2 g/dL to 11.4 g/dL in the control patients. Interestingly, Hb fell below 9 g/dL in only 4 (4%) of the control group, showing that relatively few patients ever meet the current guidelines for epoetin alfa use, Dr. Straus said.

Epoetin alfa patients reported a significant improvement (P = .036) in total FACT-An score, in addition to the anemia (P = .047), physical well-being (P = .003), and fatigue (P = .032) subscales.

Decreases in LASA daily activities and energy scores correlated only with progressive disease status, not with treatment. Epoetin alfa treatment and low baseline hemoglobin were associated with hemoglobin change (P < .001). "Despite the relatively small hemoglobin changes, the improvements in total FACT-An and anemia subscale scores were significantly correlated with the change in hemoglobin," Dr. Straus said.

From baseline to end of treatment, the epoetin alfa group, compared with the control group, had a significantly greater decrease in clinic visits (P = .002) and in days requiring general assistance with usual daily activities (P < .005). The epoetin alfa group had a decrease of about 5% in physician visits over the course of the study, compared with no change in the control group. Days of missed work decreased by 20% in the treated group but increased by 5% in the control group, Dr. Straus said.

"These results suggest that weekly epoetin alfa improves the sense of well- being and ability to function in patients with mild-to-moderate anemia who are receiving chemotherapy for lymphoma, CLL, or multiple myeloma," Dr. Straus said. "We have shown proof of principle that such improvement is associated with a decrease in clinic visits and an enhanced ability to continue or return to work, and this is likely to translate into an economic benefit." His group hopes to have the final analysis of this study completed by the end of 2003.