Epoetin alfa is an established treatment of anemia in patients with cancer who are receiving chemotherapy with or without radiation therapy. However, fewer data support its use in patients with cancer not currently receiving either therapy. This 16-week, open-label, nonrandomized, multicenter pilot study evaluated the clinical profile of epoetin alfa (40,000 U) administered weekly via subcutaneous injection in anemic patients with cancer not receiving chemotherapy or radiation therapy. The primary endpoint was the proportion of patients who achieved a minor (hemoglobin [Hgb] increase > or = 1-1.9 g/dL) or major (Hgb increase > or = 2 g/dL) hematologic response. The trial was temporarily suspended to amend the protocol to reflect updated package insert recommendations for target Hgb and dose adjustments. Of the 98 patients enrolled, 91 (mean age, 69.5 +/- 9.5 years; baseline Hgb level, 10.4 +/- 0.7 g/dL) were evaluated for efficacy in a modified intent-to-treat analysis. Nearly all patients (94.5% [86/91]) achieved a minor response, and the majority (80.2% [73/91]) achieved a major hematologic response at any time during the study. Mean Hgb levels increased steadily over the 12-week dosing period, with significant (P < 0.001) increases from baseline observed as early as week 2. Only one patient required a transfusion. Epoetin alfa was safe and well tolerated.