Chemotherapy-induced Anaemia Clinical Trial
Official title:
Combination With Intravenous Iron Supplementation or Doubling Erythropoietin Dose for Patients With Chemotherapy-induced Anaemia Inadequately Responsive to Initial Erythropoietin Treatment Alone
A multicentre, randomized, open-label, parallel-group, active controlled non-inferiority study
Chemotherapy-induced anaemia (CIA) is a significant health problem for patients with cancer
undergoing chemotherapy, causing fatigue and reducing quality of life (QoL). Up to 75% of
cancer patients undergoing chemotherapy and/or radiotherapy reportedly experience
mild-to-moderate anaemia (defined by a haemoglobin level of 9 to 11 g/dL). In clinical
trials, erythropoietins (EPOs) have been shown to increase haemoglobin levels and improve
anaemia and QoL in cancer patients. However, recent meta-analyses have highlighted possible
safety issues regarding EPO exposure. Preclinical studies have pointed towards the role of
EPO in augmenting tumorigenesis, metastasis, risk of thrombosis, and drug resistance in
certain tumor types (e.g., breast cancer), as it can activate important antiapoptotic
pathways targeted by current antineoplastic therapies, thus counteracting their effects.
Current guidelines in western countries and China recommend restricted usage of EPOs and
reduction / prevention of blood transfusions in the treatment of cancer-induced anaemia.
However, the inadequate response to erythropoietic therapy has not been well-characterized
through rigorous studies and hence remains poorly handled in routine clinical practice. A
major cause for not responding to EPO treatment is likely functional iron deficiency (FID),
which is defined as a failure to provide iron to the erythroblasts despite sufficient iron
stores. Patients with FID require supplementation of usable iron to optimize response to
erythropoietic therapy, which might not be accomplished with oral iron. In a recent
prospective, open-label trial, patients receiving epoetin alfa for CIA who were treated with
IV iron dextran had a significantly greater Hb response compared with those receiving oral
iron. Meanwhile, in patients with CIA and no iron deficiency, IV iron supplementation
significantly reduced treatment failures to darbepoetin without additional toxicity.
However, whether that IV iron supplementation increases the risk of disease progression,
incidence of thrombosis and heart failure as well as iron overload, is under careful
investigation. Though the association between IV iron and serious AEs and mortality remains
unclear, Zitt et al. found that the use of IV iron was associated with a 22% reduction in
mortality. Therefore, investigators designed this multicentre, randomized trial to
investigate EPOs in combination with IV iron with regard to an increase of Hb levels in
patients who have inadequate responses to initial treatment with routine doses of EPOs.
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Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment