John:  Anemia is one of the common side effects of cancer chemotherapy and it can be treated by a group of drugs called Erythropoiesis-stimulating agents. However, these are not always successful on their own and iron might also be added. A new Cochrane Review in February 2016 examines the evidence for its effectiveness and lead author, Rahul Mhaskar, from the University of South Florida in the USA, tells us more in this Evidence Pod.

Rahul: A large proportion of cancer patients undergoing chemotherapy develop chemotherapy-induced anemia. In people undergoing myelosuppressive chemotherapy or radiation therapy, or both, it can be as high as 90%, and it’s about 60% in people with solid tumors and lymphomas. Chemotherapy-induced anemia can lead to fatigue, weakness, and dyspnea, and consequently a lower quality of life, so it is important to find ways to treat it.
One technique is to give the patient a transfusion of red blood cells but we were interested in an alternative, the erythropoiesis-stimulating agents (commonly known as ESAs). These are man-made proteins that stimulate the production of red blood cells in bone marrow when the oxygen level in the blood goes down. However, about half of patients do not benefit from ESAs and the drugs have been associated with an increased risk of thromboembolic events. Hence, iron has been proposed as an adjunct to ESAs in the management of chemotherapy-induced anemia. We wanted to investigate whether this is worthwhile and the evidence looks promising.
We included eight studies that had tested the role of iron in the management of chemotherapy-induced anemia in cancer patients receiving ESAs. These had randomized a total of nearly 2100 patients to either ESA plus iron or ESA alone. We didn’t find any trials in which iron alone was compared with ESA alone in people with chemotherapy-induced anemia.
There was a beneficial effect of iron supplementation to ESAs compared with ESAs alone on hematopoietic response and mean change in hemoglobin levels, which did not seem to increase with increasing dose of iron when we looked at this using a statistical technique called meta-regression. However, the benefit seemed to be mainly in those trials that used intravenous iron, rather than those in which patients were given the iron orally.
None of the trials reported data on overall survival and in the trials that investigated quality of life, there was no evidence for a difference when iron was added to ESAs. There were no treatment related deaths and other common adverse events, which included vomiting, asthenia, and leukopenia, were similar whether or not the patient was given iron. And, because the included studies had relatively short follow-up, of up to 20 weeks, they provide no evidence on the long-term effects of iron supplementation.
In summary, our systematic review shows that addition of iron to ESAs improves hematopoietic response, reduces the need for red blood cells transfusions, increases hemoglobin levels, and appears to be well tolerated by cancer patients with chemotherapy-induced anemia. The subgroup analyses suggest the superiority of intravenous iron over oral iron.

John: If you'd like to read more about this and other subgroup analyses or the findings of the review, you can find it with a simple search for 'iron and cancer' at Cochrane Library dot com.