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Abstract Introduction  Anemia is frequently associated with cancer due to the disease itself and antineoplastic treatments. This open-label, uncontrolled, multi-center study evaluated the effects of once-weekly (qw) epoetin alfa 40,000 IU on hemoglobin (Hb) levels and quality of life (QoL) in anemic patients receiving chemotherapy for solid tumors. Materials and methods  A total of 522 patients with Hb level ≤12 g/dL received epoetin alfa 40,000 IU qw subcutaneously for 9–20 weeks to reach and maintain Hb range of 12–14 g/dL. QoL was assessed with the Functional Assessment of Cancer Therapy-Anemia (FACT-An [anemia sub-scale]) and Cancer Linear Analogue Scale (CLAS) at study entry, after two chemotherapy cycles, and at study end. Results  Mean baseline Hb was 10.43 g/dL. Hb increases (g/dL) from baseline after 4, 8, 12 weeks and at study end were 1.07, 1.77, 1.92 and 1.71 g/dL, respectively. Response rates (Hb increase ≥1 and ≥2 g/dL during trial) were 81% and 61%, respectively. Mean increases in the FACT-An score from baseline (mean 55.4) were 3.1 after two chemotherapy cycles and 3.3 at study end; mean increases in the CLAS score from baseline (58.4 mm) were 5.9 mm after two chemotherapy cycles and 6.5 mm at study end. Discussion  The greatest QoL increase was recorded when patients approached Hb level of 12 g/dL, independent of the baseline Hb level. Hb changes from baseline to trial end were related to corresponding changes in the FACT-An score. A positive correlation was also observed in patients with progressive disease. Adverse events were essentially those associated with chemotherapy. Incidence of thrombovascular events (6.7%) did not differ from the expected standard treatment in cancer patients. Epoetin alfa 40,000 IU qw increased Hb levels and improved or preserved QoL. [ABSTRACT FROM AUTHOR]