Darbepoetin Alfa Improves Fatigue

[RandyW]

Darbepoetin alfa appears to reduce fatigue in cancer patients with chemotherapy-induced anaemia by increasing their haemoglobin levels, according to an analysis of data from 3 studies presented at the American Society of Clinical Oncology (ASCO) 44th Annual Meeting.

"We found a direct relationship between darbepoetin alfa and haemoglobin, and we found an indirect relationship between darbepoetin alfa and improvements in fatigue," said lead investigator Margaret Vernon, PhD, United Biosource Corporation, Bethesda, Maryland.

Darbepoetin alfa is used commonly to reduce the need for transfusion associated with chemotherapy-induced anaemia.

"The impact of darbepoetin alfa on fatigue has been difficult to examine in placebo-controlled trials due to the indirect mediating effect of haemoglobin and the confounding effect of transfusions," noted the researchers.

In their study, presented on May 31, Dr. Vernon and colleagues evaluated data from 3 placebo-controlled, phase 3 trials to determine the effects of darbepoetin alfa on fatigue in cancer patients with chemotherapy-induced anaemia.

To estimate growth over a period of time the researchers applied latent-growth modelling, which allowed them to make simultaneous examinations of direct and indirect effects incorporating data from all time points in the studies.

They analysed the data from the 3 trials separately -- 2 trials of lung cancer patients (n = 596 and n = 314) and 1 trial of 349 patients with lymphoproliferative malignancies.

Fatigue was measured using the patient-completed Functional Assessment of Cancer Therapy Fatigue (FACT-F) subscale, and the direct and indirect effect of darbepoetin alfa on fatigue was measured using multiple-regression and latent-growth modelling, controlling for transfusions and baseline health status.

Subjects who received darbepoetin alfa had higher haemoglobin levels compared with subjects on placebo, after controlling for transfusions (lung P < .05; lymphoproliferative P < .05).

Subjects with higher haemoglobin levels during the trials also had less fatigue (lung P < .05; lymphoproliferative P < .05).

The overall effect of darbepoetin alfa on fatigue outcomes showed that darbepoetin alfa accounted for 16% to 21% of the explained variance in fatigue outcomes, which was calculated by multiplying the effect of darbepoetin alpha by the effect of haemoglobin on fatigue.

Using latent-growth modelling, the researchers found that among patients in the 2 lung cancer trials analysed, darbepoetin alfa resulted in a mean FACT-F change of 2.3 and 2.9 points, which approached the minimally important difference of 3 points for FACT-F. The mean change in FACT-F was 3.5 points for subjects with lymphoproliferative disease who received darbepoetin alfa.

"When controlling for transfusions and baseline health status, DA [darbepoetin alfa] was found to have an indirect effect on fatigue mediated by Hb [haemoglobin] increase in patients with lung and lymphoproliferative malignancies," the researchers concluded. "Results suggest that analyses that incorporate the mechanism of DA action may better quantify the benefits of DA on patient-reported fatigue and the mediating effect of Hb increase on fatigue improvement."

Funding for this study was provided by Amgen Inc.

[The Effect of Darbepoetin Alfa on Patient-Reported Fatigue in Cancer Patients: Results From Three Phase III Clinical Trials. Abstract 9616]