Ferric Carboxymaltose Alone or Combined with Erythropoietin Allows a Modest Increase in Hemoglobin for the Treatment of Cancer-Related Anemia in Advanced Cancer Patients
Authors: Blanc Cécile , Dujaric Marie-Eglantine , Giard Caroline , Asselain Bernard , Ferry Isabelle , Glaisner Sylvie , Callens Céline , Vargaftig Jacques 
Published: October 2019

Abstract
Background: Cancer-related anemia is a very frequent condition of complex physiopathology which impacts heavily on quality of life, morbidity and mortality of cancer patients. Treatment options are limited to red blood cell transfusion, erythropoiesis stimulating agents (ESA) and intravenous (IV) iron administration alone or combined. IV iron administration is being increasingly advocated over transfusion and ESA because of reduced costs and satisfactory safety profile. Efficacy was mainly evaluated in selected early phase cancer patients. Concerns about infection rates and tumor growth/promotion by systemic iron administration were not addressed.
Aim of the study: To evaluate the efficacy of ferric carboxymaltose alone or combined with erythropoietin in a French cohort of advanced cancer patients
Methods: This retrospective single-center study is derived from a pharmacy database recording 139 ferric carboxymaltose infusions for 137 patients in a cancer center between February 2012 and December 2013. Median age is 66 y (38-91), sex ratio is 81% F/M, 84% of patients are metastatic, distribution of primary tumor sites is: 52% breast, 22% gynecologic, 17% gastrointestinal, 9% others. Hematologic patients were excluded. Renal function is satisfactory for all patients. 78 patients are treated with iron alone, 61 with iron + ESA. Baseline median laboratory parameters are: 9.7 g/dl (7.2-14.1) for hemoglobin (Hb), 22 mg/l (0.06-305) for CRP, 391 µg/l (21-4248) for ferritin, 0.14% (0.03-0.32) for transferrin saturation. There is no statistical difference between the 2 groups for population and laboratory data. 77% and 97% of iron alone and combined group patients receive concomitant chemotherapy, respectively.
Results: Median increase in Hb from baseline after 1 and 3 months of treatment for the total cohort is +0.8 g/dl (-2.9-+5.7) and +0.1 g/dl (-3.9-+4) respectively. Yet of modest magnitude, these 2 increments are statistically significant (p<10-4, Wilcoxon test). Median ferritin increase after 1 month is +454 µg/l (+19-+829) (data is only available for 32/139 IV iron treatments). Increase in Hb from baseline is not statistically different between the 2 treatment groups after 1 month (+0.6 g/dl for iron alone vs. +0.9 g/dl for combined treatment) but favors iron alone group over combined group after 3 months (+0.4 g/dl vs. -0.2 g/dl, p=0.02, Wilcoxon test). No correlation between baseline laboratory parameters and hemoglobin increase at 1 and 3 months is found for the total cohort and for each treatment group. One exception is baseline transferrin saturation and hemoglobin increase at 1 month for the total cohort which are inversely correlated (p=0.03, Pearson’s correlation coefficient). No grade III-IV side effects were recorded during ferric carboxymaltose infusions.
Conclusions: Carboxymaltose either alone or combined with ESA was well tolerated in an advanced cancer cohort. The 2 treatments could increase Hb at 1 month without difference between them. The increments obtained for Hb although statistically significant do not seem to be clinically relevant when considering potential dangers such as infection rate and potential iron diversion by tumor metabolism to promote cancer growth. Prospective controlled studies are warranted to evaluate the true clinical benefit of IV iron in cancer patients balancing Hb increase, quality of life and tumor evolution.

Disclosures
No relevant conflicts of interest to declare.