Epoetin alfa (EPO) 40,000–60,000 U SC once weekly (QW) has been shown to increase hemoglobin (Hb) by ~2 g/dL after 8-12 wks in anemic patients (pts) with cancer receiving chemotherapy (CT). The proportion of pts achieving a hematologic response (HR; Hb ≥12 g/dL and/or Hb increase ≥2 g/dL from baseline [BL]) at this dosage was ~70%. It was hypothesized that higher initiation doses of EPO may result in earlier HR and improved HR rates. This nonrandomized, open-label, pilot study was designed to investigate the safety and efficacy of EPO 80,000 U SC QW for up to 12 wks in anemic (Hb ≤11 g/dL) pts with nonmyeloid malignancies undergoing CT. If Hb increased to >13 g/dL, EPO was held until Hb ≤12 g/dL, then dose reduced by 20,000 U. Dose was similarly reduced if Hb increased >1.3 g/dL in 2 wks. Primary endpoint was proportion of pts with a major response, defined as HR. Secondary endpoints included proportion of pts with a minor response (Hb increase ≥1 g/dL but <2 g/dL from BL), time to major or minor response, Hb over time, and transfusions. Response rates were independent of RBC transfusion within previous 28 days. Weekly Hb was analyzed using last value carried forward method to impute missing Hb values; Hb values within 28 days following an RBC transfusion were excluded. Sixty-nine pts were enrolled, 46 (67%) of whom completed through the final study visit. All 69 pts (64% women; mean age 62 y; 83% ECOG PS 0–1) received ≥1 dose of study drug and were evaluable for safety; 68 pts were evaluable for efficacy (modified intent-to-treat population: ≥1 post-BL Hb or transfusion value). Most common tumor types were breast (28%), colorectal (16%), lung (16%), and ovarian (13%). Mean BL Hb was 10.1 ± 0.8 g/dL (n=64). Thirty-seven (54%) pts had ≥1 dose reduction and 33 (48%) pts had ≥1 dose held. Median time to first dose reduction or hold was 28 days (n=48) and the mean dose was approximately 62,600 U/wk. Pts were evaluated for best response, of which 49 (72%) pts achieved a major response and 6 (9%) achieved a minor response. Major and minor responses were achieved after a median of 6.0 wks (n=49) and 3.0 wks (n=44; includes pts with minor response at best or minor response followed by major response), respectively. Mean changes in Hb after 4 wks, 8 wks, and at final value were 1.0 ± 1.4 g/dL (n=60), 1.7 ± 1.4 g/dL (n=62), and 2.0 ± 1.4 g/dL (n=62), respectively. Six (9%) pts were transfused at any point during the study; 2 (3%) were transfused after day 28. Adverse events (Aes) were reported in 65 (94%) pts; most commonly reported Aes were nausea and neutropenia. Nineteen (28%) pts had serious Aes. Six (9%) pts had Aes that led to study discontinuation, 4 of whom died. Five (7%) pts were diagnosed with a total of 6 clinically relevant thrombotic vascular events (3 deep venous thromboses, 2 pulmonary emboli, 1 cardiac arrest); none was considered related to study drug. These pilot data showed that this EPO dosing regimen increased Hb by 1.7 g/dL after 8 wks in pts with cancer and anemia receiving CT. The HR rate of ~70% and safety profile observed with EPO 80,000 U SC QW were similar to historical results from studies of EPO 40,000 U SC QW with dose escalation to 60,000 U SC QW, perhaps related to frequent dose reductions and holds in the present study or a potential plateau in response at doses greater than 40,000–60,000 U SC QW.

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