OBJECTIVES: To evaluate the clinical significance of a greater area under the hemoglobin change curve (Hb AUC) value during epoetin alfa (EPO) treatment. METHODS: Datasets from two EPO trials were used (Study 1: N = 2,964; Study 2: N = 2,289). Initial EPO regimens were: Study 1: 40,000IU once weekly (QW), Study 2: 10,000IU thrice weekly (TIW). Each study allowed for potential dose escalation to 60,000IU QW and 20,000IU TIW respectively. Patients were ³18 years, had a baseline Hb of £11g/dL, and received concomitant chemotherapy. Outcome measures included: blood transfusions, quality of life (QoL) measured by Linear Analog Scale Assessment and Functional Assessment of Cancer Therapy Anemia and Fatigue, drug utilization and hematopoietic response. All missing values were imputed based on a last-value-carried-forward principle. Hb AUC values (g/dL) from baseline to 16 weeks were stratified into five groups established based on data frequency distributions and clinical judgment (Hb AUC 1: < 11; Hb AUC 2: 11 - < 18; Hb AUC 3: 18 - < 25; Hb AUC 4: 25 - <32; Hb AUC 5: > 32). RESULTS: Mean Hb AUCs were similar (Study 1: 19.7 g/dL, Study 2: 21.3 g/dL). For Hb AUC groups 1-5 respectively, the following significant trends were observed for patients with greater Hb AUC values: decreased transfusion use (%) (Study 1: 41, 24, 15, 14, 10; Study 2: 46, 33, 24, 21, 15), increased QoL across all domains, reduced weekly dose (IU) (Study 1: 45,934, 45,130, 42,596, 41,021, 39,478; Study 2: 38,643, 37,752, 35,011, 33,853, 31,459) and improved hematopoietic response (%) (Study 1: 13, 54, 85, 98, 100; Study 2: 8, 52, 79, 96, 100). CONCLUSIONS: Hb AUC is a comprehensive efficacy measure reflecting Hb change over the entire treatment course. Greater Hb AUC values are associated with a reduction in transfusion requirements, improved QoL and drug utilization outcomes, confirming its clinical significance.