Every-Three-Week (Q3W) Maintenance Dosing of Epoetin Alfa in Anemic Cancer Patients Receiving Chemotherapy: 60,000 U SC QW to Target Hb 12 g/dl, Followed by 80,000 U SC Q3W.

The efficacy of epoetin alfa (EPO) 40,000 U SC once weekly (QW) has been established in clinical studies in anemic patients (pts) with cancer receiving chemotherapy (CT). Higher starting doses of EPO may increase initial hemoglobin (Hb) response and subsequent less frequent maintenance dosing may improve dosing flexibility for pts and health care providers. This ongoing, open-label, multicenter, 24-week (wk) study was designed to evaluate the efficacy and safety of EPO at a starting dose of 60,000 U SC QW to a target Hb of 12 g/dL in the Initiation Phase (IP; maximum of 12 wks), followed by 80,000 U SC every 3 wks (Q3W) in the Maintenance Phase (MP) to maintain Hb in the range 11.5–12.5 g/dL. Eligible pts were ≥18 years with nonmyeloid malignancy, had baseline (BL) Hb <11 g/dL, and were scheduled to receive CT Q3W for ≥15 wks. Pts who achieved Hb ≥12 g/dL during the IP subsequently entered the MP; however, pts did not receive the first Q3W maintenance dose until start of the next Q3W CT cycle. Pts were withdrawn if Hb decreased to <11 g/dL during the MP. The primary endpoint was proportion of pts in the IP who achieved an Hb ≥12 g/dL or an Hb increase ≥2 g/dL from BL. Secondary endpoints included Hb increase ≥1 g/dL but <2.0 g/dL from BL in IP, maintenance of mean Hb 11.5–12.5 g/dL in the MP, maintenance of mean Hb >11.0 g/dL but <11.5 g/dL in MP, Hb over time, and transfusions. All Hb and response rates were independent of RBC transfusion within the previous 28 days. Study enrollment was terminated at 115 pts. In this preliminary analysis, the first 69 pts (mean age, 62 years; 65% women; 87% ECOG 0-1) enrolled and who received ≥1 dose of study drug were evaluable for safety and efficacy. Mean BL Hb was 10.2 ± 0.8 g/dL. The proportion of pts in the IP who achieved an Hb ≥12 g/dL or an Hb increase ≥2 g/dL from BL was 74% (49/69). The proportion of pts in the IP with an Hb increase ≥1 g/dL but <2 g/dL from BL was 9% (6/69). Forty-one (59%) pts entered the MP after a median of 5.0 wks in the IP and spent an average of 7.1 wks in the MP. Of these pts, 33 (80%) maintained an average Hb of 11.5–12.5 g/dL and 3 (7%) maintained an average Hb >11.0 g/dL but <11.5 g/dL over the course of the MP. During the MP, mean Hb was 12.1 ± 0.6 g/dL at entry, 11.8 ± 1.0 g/dL (n=15) after 8 wks of Q3W dosing, and 11.6 ± 1.1 g/dL (n=38) at final value. Eleven (27%) pts were withdrawn during the MP because Hb decreased to <11 g/dL. EPO dose was reduced in 25% (17/69) of pts in the IP and in 39% (16/41) of pts in the MP due to Hb >13 g/dL or Hb increase >1.3-g/dL in 2 wks. Thirty-five percent (24/69) of pts had a dose of EPO held at any time during the study for Hb >13 g/dL or another reason. Five (7%) pts were transfused after study day 28. Twenty-six (38%) pts experienced serious adverse events (AEs). Eight (12%) pts experienced a clinically relevant thrombovascular event. Two (3%) pts discontinued due to AEs. Nine (13%) pts died during the study or within the 90-day follow-up period. These preliminary data suggest that initial dosing of EPO 60,000 U QW is associated with a hematopoietic response rate (Hb ≥12 g/dL or Hb increase ≥2 g/dL from BL) of ~75% in pts with cancer and anemia receiving CT, similar to the response rate reported historically for EPO 40,000 U SC QW with dose escalation to 60,000 U SC QW. In addition, among pts who achieved a target Hb ≥12 g/dL with QW dosing and then received Q3W maintenance dosing, EPO 80,000 U SC Q3W maintained mean Hb above 11 g/dL in >85% of pts.