Efficacy of Intravenous Iron Replacement for Chemotherapy-Induced Anemia: A Prospective Phase II Pilot Study

Abstract

Background: Iron deficiency anemia (IDA) is a common cancer-related complication, and intravenous (IV) iron administration has been reported to be effective in treating chemotherapy-induced anemia. This study aimed to evaluate the efficacy of IV iron administration without erythropoiesis-stimulating agents for anemia in cancer patients and to identify biomarkers for hemoglobin (Hb) response to predict the need for iron supplementation. Methods: This prospective single-arm phase II study enrolled solid cancer or lymphoma patients without bone marrow involvement. Patients received injection of IV ferric carboxymaltose (1000 mg) on the first day (visit 1) of chemotherapy or target therapy. Hb response, defined as an increase of ≥1·0 g/dL Hb, was assessed at visits one, two, and three. To identify predictive biomarkers of Hb response, transferrin saturation (TSAT) and levels of soluble transferrin receptor, hepcidin, erythropoietin, interleukin-6, and C-reactive protein were assessed at each visit. Findings: Of the 103 enrolled patients, 92 were eligible for analysis. Hb response was observed in 36 (39.1%), 53 (57.6%), and 61 (66.3%) patients at visits one, two, and three, respectively. After excluding 19 patients (20.6%) with absolute IDA, the Hb response rate was 83.5% (61/73). Regarding anemia-related biochemical parameters, Hb responders had significantly lower hepcidin levels than Hb non-responders (13.5 vs. 35.2 ng/mL; p=0.007). Upon comparing Hb response to the baseline hepcidin level, the low-hepcidin group contained significantly more responders than the high-hepcidin group (58/61 [95.1%] vs. 3/61 [4.9%]; p=0.002), based on a cutoff value of 34.1 ng/mL. Interpretation: IV iron supplementation increases Hb levels without serious adverse events in cancer patients receiving anticancer treatment. Furthermore, hepcidin is a useful biomarker for predicting functional IDA in cancer patients. These findings, however, need further validation. Funding: The study drug was provided by JW Pharmaceutical, Seoul, Republic of Korea. Declaration of Interest: The authors declare that they have no conflicts of interest concerning this article. Ethical Approval: The protocol was reviewed and approved by the institutional review board of Samsung Medical Center (IRB No. 2015-01-011), and the trial was conducted in accordance with the Declaration of Helsinki.