title: Combination with intravenous iron supplementation or doubling erythropoietin dose for patients with chemotherapy-induced anaemia inadequately responsive to initial erythropoietin treatment alone: study protocol for a randomised controlled trial.
abstract: Erythropoietin (EPO) is a commonly used option in the treatment of chemotherapy-induced anaemia (CIA). However, ∼30-50% of patients fail to achieve an adequate response after initial treatment. Prior studies have demonstrated that intravenous iron might synergistically improve therapeutic response to EPO treatment in this patient population.
  
  
  
  We will perform this multicentre, randomised, open-label, parallel-group, active controlled non-inferiority study to compare the two combination therapies of EPO plus intravenous iron regimen versus doubling the dose of EPO in patients with CIA who have an inadequate response to initial EPO treatment at a routine dose. A total of 603 patients with an increase in haemoglobin (Hb) <1 g/dL will be enrolled and randomised to one of the three study treatment groups at a 1:1:1 ratio Group 1: EPO treatment at the original dose plus intravenous iron dextran 200 mg every 3 weeks (Q3W) for 15 weeks; Group 2: EPO treatment at the original dose plus intravenous iron dextran 100 mg, twice a week for 5 weeks; Group 3: the control group, doubling the EPO dose without preplanned iron supplementation. The primary outcome measure to compare is the Hb response rate at week 15 and the secondary end points involve therapeutic blood transfusions. Time-to-progression, adverse events and quality of life will also be evaluated.
  
  
  
  All participants will provide informed consent; the study protocol has been approved by the independent ethics committee of Shanghai East Hospital. This study would clearly demonstrate the potential benefit of combining epoetin treatment with intravenous iron supplementation. Findings will be shared with participating hospitals, policymakers and the academic community to promote the clinical management of CIA in China.
  
  
  
  NCT02731378.
authors.affiliation: Department of Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Department of Gastrointestinal Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Gao
authors.affiliation: Department of Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Tu
authors.affiliation: Department of Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Gastrointestinal Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Department of Gastrointestinal Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Qixin
authors.initials: Q
authors.lastname: Jiang
authors.affiliation: Department of Gynecology, Jing'an District Centre Hospital of Shanghai (Huashan Hospital Fudan University Jing'an Branch), Shanghai, China.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Zhan
authors.affiliation: Department of Orthopaedics, Changzheng Hospital, Shanghai, China.
authors.forename: Jiangming
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Gastrointestinal Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Chuangang
authors.initials: C
authors.lastname: Fu
authors.affiliation: Department of Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Gao
mesh_terms: D000293:Adolescent; D000328:Adult; D000740:Anemia / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D002681:China; D002985:Clinical Protocols; D019587:Dietary Supplements; D004357:Drug Synergism; D004921:Erythropoietin / Q000008:administration & dosage / Q000627:therapeutic use*; D006397:Hematinics / Q000008:administration & dosage / Q000627:therapeutic use*; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D007501:Iron / Q000008:administration & dosage / Q000627:therapeutic use*; D007505:Iron-Dextran Complex / Q000008:administration & dosage / Q000627:therapeutic use*; D012107:Research Design
chemical_list: D000970:Antineoplastic Agents; D006397:Hematinics; D006454:Hemoglobins; D004921:Erythropoietin; D007505:Iron-Dextran Complex; D007501:Iron
keywords: chemotherapy-induced anaemia; erythropoietin; inadequately responsive; iron supplementation; randomized controlled trial