Darbepoetin Alfa With or Without Iron in Treating Anemia Caused By Chemotherapy in Patients With Cancer

OBJECTIVES:

Primary

• To compare the effects of IV iron, oral iron, or placebo in combination with darbepoetin alfa on the hematopoietic response rate, defined as a hemoglobin increment of ≥ 2.0 g/dL from baseline or achievement of hemoglobin of ≥ 11 g/dL in the absence of red blood cell transfusions (RBC) in the preceding 28 days of the treatment period, in cancer patients with chemotherapy-associated anemia.

Secondary

• To compare the effects of these regimens on the mean hemoglobin increment from baseline to weeks 7 and 16 in these patients.
• To compare the effects of these regimens on the percentage of patients maintaining an average hemoglobin level within the American Society of Hematology/American Society of Clinical Oncology (ASH/ASCO)and National Comprehensive Cancer Network(NCCN) guideline-based target hemoglobin range (11-13 g/dL), once achieving a hemoglobin of ≥ 11 g/dL from week 1 to week 16 in the absence of RBC transfusions in the preceding 28 days of the treatment period.
• To compare the effects of intravenously (IV) iron, oral iron, or placebo on the response to darbepoetin alfa, in terms of time to achieving hemoglobin levels of ≥ 11g/dL.
• To compare the effects of these regimens on the percentage of patients who require RBC transfusions and the total transfusion needs.
• To compare the effects of these regimens on the change in hemoglobin week by week.
• To compare the effects of these regimens on quality-of-life changes from baseline to weeks 7 and 16.
• To identify if patients with inflammation (as indicated by elevated C-reactive protein (CRP) and serum hepcidin levels or low soluble transferrin receptor (sTfR)/log ferritin ratios) respond differently to darbepoetin alfa and iron therapy than patients without inflammation.

OUTLINE: Patients are stratified according to severity of anemia (mild [hemoglobin ≥ 9.5 g/dL] vs severe [hemoglobin < 9.5 g/dL]), treatment with a platinum-containing regimen (yes vs no), and gender. Patients are randomized to 1 of 3 treatment arms.

• Arm I: Patients receive darbepoetin alfa subcutaneously and sodium ferric gluconate complex IV over 90 minutes on day 1.
• Arm II: Patients receive darbepoetin alfa as in arm I and oral ferrous sulfate once daily on days 1-21.
• Arm III: Patients receive darbepoetin alfa as in arm I and oral placebo once daily on days 1-21.

In all arms, treatment repeats every 21 days for up to 15 weeks in the absence of unacceptable toxicity.

Patients complete quality-of-life (QOL) questionnaires in weeks 1, 7, and 16.

DISEASE CHARACTERISTICS:

• Diagnosis of a non-myeloid cancer (other than non-melanomatous skin cancer)
• Receiving or scheduled to receive chemotherapy (biological agents, such as small molecules/tyrosine kinase inhibitors and antibody-based therapies, are allowed)
• Has chemotherapy-related anemia (hemoglobin < 11 g/dL)

• No anemia known to be secondary to gastrointestinal bleeding or hemolysis
• No anemia known to be secondary to vitamin B12 or folic acid deficiency

+ Vitamin B12 and folic acid deficiency must be ruled out if the mean corpuscular volume (MCV) is > 100 fL

• No anemia secondary to chemotherapy-induced myelodysplastic syndromes
• No primary hematologic disorder causing moderate to severe anemia (e.g., congenital dyserythropoietic anemia, homozygous hemoglobin S disease or compound heterozygous sickling states, or thalassemia major)

• Carriers for these disease states are eligible
• No first-degree relative with primary hemochromatosis (unless the patient has undergone HFE genotyping and was found to have at least one wild-type allele, while the proband in the family demonstrated to have either the common C282Y or H63D mutation)

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Ferritin > 20 mcg/L (i.e., not obviously iron deficient)
• ALT or AST < 5 times upper limit of normal
• Alert, mentally competent, and able to sign informed consent
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 3 months after completion of study treatment
• Willing or able to be randomized and undergo study treatment
• Willing or able to fill out quality-of-life forms
• No uncontrolled hypertension (i.e., systolic blood pressure [BP] ≥ 180 mm Hg or diastolic BP ≥ 100 mm Hg)
• No history of uncontrolled cardiac arrhythmias
• No pulmonary embolism or deep venous thrombosis within the past year (unless the patient is on anticoagulation therapy and planning to continue it during study participation)
• No known hypersensitivity to darbepoetin alfa, erythropoietin, mammalian cell-derived products, iron, or human albumin
• No seizures within the past 3 months
• No gastrointestinal conditions expected to cause significant impairment of oral iron, such as untreated celiac disease or amyloidosis involving the gut - Patients with celiac disease who are adhering to a gluten-free diet are eligible

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• More than 3 months since prior darbepoetin alfa, epoetin alfa, or any investigational forms of erythropoietin (e.g., gene-activated erythropoietin or novel erythropoiesis-stimulating protein)
• More than 1 year since prior peripheral blood stem cell or bone marrow transplantation
• More than 2 weeks since prior red blood cell transfusions
• More than 14 days since prior major surgery
• No prior gastrectomy or resection of > 100 cm of small intestine
• Not planning to undergo stem cell or bone marrow transplantation within the next 6 months