Intravenous Ferric Gluconate (FG) for Increasing Response to Epoetin (EPO) in Patients with Anemia of Cancer Chemotherapy - Results of a Multicenter, Randomized Trial.

A significant proportion of cancer patients receiving chemorx will present with or develop anemia. The cause of this anemia is often the inflammatory cytokine-mediated anemia of chronic disease associated with cancer and/or chemorx. We conducted a prospective randomized controlled multicenter trial in anemic cancer patients on chemorx to see if no iron, oral iron, or IV iron, affects Hb response to EPO. Major inclusion criteria: pt about to start cycle of chemorx, eligible for EPO therapy, Hb <11 g/dL, with ferritin > 100 ng/mL and/or transferrin saturation (TSAT) >15%. Major exclusion criteria: recent transfusion, EPO or IV iron use, active infection, anemia from other causes. All pts received 40,000 U epoetin alfa SQ/Wk for first 4 wks, after which dose adjustments permitted for remainder of study period. All pts received cytotoxic chemorx. Pts returned weekly for 8-week treatment period with follow-up visits at wks 10 and 12. Safety population includes all pts exposed to study drug (n=187). Intent-to-treat (ITT) population is pts with at least 1 post-baseline Hgb evaluation prior to transfusion (n=180). Evaluable population consists of ITT pts with no major protocol deviations, who completed ≥7 weeks of the study, received at least 4 doses of EPO, and according to group, ≥ 7 doses of FG, or ≥67% of oral Fe (n=129). Treatment groups compared using ANCOVA model with multiple comparison adjustment. 187 Pts (69% female, mean age 64.4 yrs) were randomized to: no Fe, PO FeSO4 325 mg tid, or FG 125 mg iv weekly for 8 wks. Most common cancers were lung (29.9%) and breast (18.2%). There were no significant differences between groups in mean baseline Hb (10.2g/dL), TSAT (31.3%), serum ferritin (421 ng/mL), reticulocyte hemoglobin content (CHr, 34.2 pg). 95% of pts had baseline ferritin >100ng/mL. Efficacy results are presented for the Evaluable population. Oral iron compliance was excellent at 93.3% of tablets dispensed. 73% of the FG group achieved a Hb increase ≥2g/dL vs 46% for oral iron (p=.0099) and 41% for no iron groups (p=.0029). This difference was most pronounced in patients with baseline TSAT <20% (94% of whom had baseline serum ferritin >100ng/mL). Among these pts, FG group had 81% response rate vs oral iron 37% (p=.0091) and no iron pts 27% (p=.0027).

Change from Baseline - Evaluable Population

Overall 93.6% of pts experienced at least 1 adverse event, evenly distributed among all 3 treatment groups. 19 pts (31.1%) in the oral iron group experienced a drug related adverse event, 4 leading to study discontinuation. 8 pts (12.7%) in the FG group experienced a drug related adverse event, 2 leading to discontinuation. In this study of anemic cancer patients on chemorx, all 3 groups responded to EPO therapy, but responses were significantly better in evaluable patients who received IV FG versus oral iron or no iron. Our data indicate FG allows the least iron restricted hematopoiesis and the best Hb responses, especially in patients with TSAT <20% and ferritin > 100, typical of anemia of chronic disease. IV FG was well tolerated.