Abstract

Background: Several measures have been used to assess the efficacy of erythropoietic agents in patients with chemotherapy-related anemia (CRA). Previous research has demonstrated the area under the 16-week hemoglobin (Hb) change curve (Hb AUC16) as a sensitive and comprehensive efficacy measure compared to traditional single time point or threshold-based measures. Higher Hb AUC16 values during epoetin alfa (EPO) therapy in patients with CRA are associated with reduced transfusion requirements, improved quality of life, increased hematologic response rates, and decreased EPO utilization. This subgroup analysis of elderly patients with CRA evaluates the clinical significance of higher Hb AUC16 values in this unique population.

Methods: Data from three, large, multicenter EPO clinical trials were evaluated. In EPO 1, patients received 10,000 Units TIW with potential escalation to 20,000 Units TIW. In EPO 2 and EPO 3 patients received 40,000 Units QW with potential escalation to 60,000 Units QW. Eligible patients for this analysis were >/=65 years, had a baseline Hb </=11g/dL, had a non myeloid malignancy and received chemotherapy with or without radiotherapy (EPO 1: N=935: EPO 2: N=1,270; EPO 3: N=269). Hb AUC16 was calculated using sequential trapezoidal methodology based on the Hb change and was stratified into quartiles to assess trends in outcome measures. Trend tests were performed to determine if the following outcomes had significant linear trends across the Hb AUC16 quartiles: proportion of patients transfused, hematopoietic response (Hb rise >/= 2 g/dL over baseline or Hb >/= 12 g/dL during study), EPO utilization, and quality of life [assessed by the Linear Analogue Scale Assessment (LASA, all studies) and the anemia subscale of the FACT-An (EPO 1 and EPO 2)].

Results: Greater Hb AUC16 values had a strong linear association with a decreasing proportion of patients transfused (p<.0001), increasing hematopoietic response rate (p<.0001), decreasing average weekly EPO dose (p<.0001), increasing LASA scores in all studies (p<.001) and FACT-An scores in EPO 1 and EPO 2 (p<.001).

Conclusions: In the elderly patient subset, greater Hb AUC16 values were associated with significant improvement in clinical outcomes including the percentage of patients transfused, hematopoietic response rates, QOL score improvements, and EPO utilization. Hb AUC16 is an objective and meaningful metric that summarizes hematologic response over the course of treatment and is associated with clinical benefits in elderly patients receiving erythropoietic therapy.

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