Randomized trial of intravenous iron supplementation in patients with chemotherapy-related anemia without iron deficiency treated with darbepoetin alpha.
OBJECTIVE
Unresponsiveness to erythropoiesis-stimulating agents, occurring in 30% to 50% of patients, is a major limitation to the treatment of chemotherapy-related anemia. We have prospectively evaluated whether intravenous iron can increase the proportion of patients with chemotherapy-related anemia who respond to darbepoetin.


METHODS
Between December 2004 and February 2006, 149 patients with lung, gynecologic, breast, and colorectal cancers and >or= 12 weeks of planned chemotherapy were enrolled from 33 institutions. Patients were required to have hemoglobin <or= 11 g/L and no absolute or functional iron deficiency. All patients received darbepoetin 150 microg subcutaneously once weekly for 12 weeks and were randomly assigned to sodium ferric gluconate 125 mg intravenously (IV) weekly for the first 6 weeks (n = 73) or no iron (n = 76). Primary end point of the study was the percentage of patients achieving hematopoietic response (hemoglobin >or= 12 g/dL or >or= 2 g/dL increase).


RESULTS
Hematopoietic response by intention-to-treat analysis was 76.7% (95%CI, 65.4% to 85.8%) in the darbepoetin/iron group and 61.8% (95%CI, 50.0% to 72.7%) in the darbepoetin group (P = .0495). Among patients fulfilling eligibility criteria and having received at least four darbepoetin administrations, hematopoietic responses in the darbepoetin/iron group (n = 53) and in the darbepoetin-only group (n = 50) were 92.5% (95% CI, 81.8% to 97.9%) and 70% (95% CI, 55.4% to 82.1%), respectively (P = .0033). Increase of hemoglobin during treatment period showed a time profile favoring darbepoetin/iron with statistically significant effect from week 5 on. The safety profile was comparable in the two arms.


CONCLUSIONS
In patients with chemotherapy-related anemia and no iron deficiency, IV iron supplementation significantly reduces treatment failures to darbepoetin without additional toxicity.
Pedrazzoli
Paolo
P
Divisione di Oncologia Medica Falck, Ospedale Niguarda Ca' Granda, Piazza Ospedale Maggiore 20162, Milano, Italy. paolo.pedrazzoli@ospedaleniguarda.it
Farris
Antonio
A
Del Prete
Salvatore
S
Del Gaizo
Filomena
F
Ferrari
Daris
D
Bianchessi
Clara
C
Colucci
Giuseppe
G
Desogus
Alberto
A
Gamucci
Teresa
T
Pappalardo
Alessandro
A
Fornarini
Giuseppe
G
Pozzi
Paola
P
Fabi
Alessandra
A
Labianca
Roberto
R
Di Costanzo
Francesco
F
Secondino
Simona
S
Crucitta
Enrico
E
Apolloni
Federica
F
Del Santo
Antonio
A
Siena
Salvatore
S
D000740:Anemia / Q000139:chemically induced / Q000188:drug therapy*; D000970:Antineoplastic Agents / Q000009:adverse effects*; D000068256:Darbepoetin alfa; D004921:Erythropoietin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D005260:Female; D006397:Hematinics / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007262:Infusions, Intravenous; D007501:Iron / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D009369:Neoplasms / Q000188:drug therapy
D000970:Antineoplastic Agents; D006397:Hematinics; D004921:Erythropoietin; D000068256:Darbepoetin alfa; D007501:Iron