Evaluating the relative efficacy of preoperative intravenous vs oral iron supplementation in reducing perioperative allogenic blood transfusions in patients of gastrointestinal malignancies with iron deficiency anemia: a randomised controlled trial

Gastrointestinal malignancies (including cancers of the esophagus, stomach, small intestine, colon, rectum and anal canal) account for a significant proportion of the total cancer burden in India (about 11 – 12 % in either sexes). Patients with gastrointestinal malignancies posted for definitive surgeries often present with anemia- mostly absolute and/or functional iron deficiency anemia – with a reported incidence of around 40% . The causes of anemia in this population are usually multi-factorial – either primarily due to the cancer (40% of the total) or, secondary to the chemotherapeutic agents used for treating the cancer (60%). Irrespective of the etiology, cancer related anemia decreases the patient’s quality of life, decreases the efficacy and tolerance to the anti-cancer therapies and often causes delay in definitive surgeries. Treatment options for pre-operative iron deficiency anemia is usually guided by the severity and the available time for optimization – and includes, oral and IV iron supplementation, erythropoietic agents and blood transfusions. Given the time-sensitive nature of onco-surgeries, often peri-operative blood transfusions are done to optimize the hemoglobin concentrations within a short period of time. However, concerns regarding transfusion-related immuno-modulation (TRIM), and circulatory overload often pose a clinical dilemma regarding the appropriateness of allogenic blood transfusions in cancer patients. Erythropoietic agents are usually contraindicated due to risks of thromboembolic events and myelodysplastic syndromes . Studies have shown a slower than desired hemoglobin buildup with oral iron supplementation along with poor tolerability. On the other hand, intravenous iron supplementation carries an inherent risk of allergic reactions ranging from urticaria to anaphylactic shock as well as iron overload due to presence of functional iron deficiency (low circulating iron levels despite adequate stores) in malignancies.

The current evidence on the comparative efficacy of intravenous vs oral iron supplementation in reducing peri-operative blood transfusions is conflicting. While, most studies show a significant improvement in hemoglobin concentrations at least 4 weeks after intravenous iron administration, the evidence regarding its efficacy in reducing perioperative blood transfusion is conflicting. Some studies report a reduction is the need for allogenic blood transfusions, while others did not report any significant difference in transfusion requirements. This contradictory data could be partly explained by the fact that different studies included variety of patient populations – both malignant and non-malignant, and some did not even ensure that the anemia is actually due to iron deficiency. Also, the time to assess the outcome measures varied from 2-4 weeks from the point of intravenous iron administration, while it is almost evident that the response to intravenous iron starts manifesting from 4 weeks onwards.

Hence, we designed this RCT to evaluate the efficacy of intravenous iron (when administered at least 4 weeks prior to elective surgeries for gastrointestinal malignancies) in patients with iron deficiency anemia in reducing the need for allogenic blood transfusion peri-operatively, as compared to our current institutional practice of administering oral iron preparations.