Darbepoetin alfa given every 1 or 2 weeks alleviates anaemia associated with cancer chemotherapy

Glaspy, John A.; Jadeja, J.; Justice, Glen; Keßler, J.; Richards, Derek; Schwartzberg, Lee S.; Tchekmedyian, N. Simon; Armstrong, Sharon; O’Byrne, J; Rossi, G.; Colowick, Alan B.

doi:10.1038/sj.bjc.6600465

Cited by 162 publications

(95 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Once weekly dosing also provided a convenience factor for patients. For further patient convenience, ESAs with less frequent dosing regimens (i.e., administered once every 2 weeks or once every 3 weeks) were also developed [21,22]. However, higher ESA doses (60,000 -80,000 IU) are needed with this expanded time interval to maintain target Hb levels.…”

Section: Recombinant Human Epomentioning

confidence: 99%

Anemia Management in Oncology and Hematology

2009

View full text Add to dashboard Cite

Anemia is frequent in cancer patients and its incidence increases with chemotherapy. The probability of requiring transfusions also increases with chemotherapy. Anemia negatively impacts survival and accentuates fatigue in cancer patients. Cancer promotes inflammatory cytokine production, which suppresses erythropoiesis and erythropoietin (EPO) production. Erythropoiesis-stimulating agents (ESAs) improve erythropoiesis and reduce transfusion needs in anemic cancer patients receiving chemotherapy. However, meta-analyses have shown an increased risk of thromboembolic (TE) events with ESA use during chemotherapy, but not increased on-study mortality or reduced overall survival. Three reasons have been proposed to explain why ESAs might have adverse effects in anemic cancer patients: tumor progression due to stimulation of tumor cell EPO receptors; increased risk of TE; and reduced survival. However, erythropoietin is not an oncogene, nor is the EPO receptor. It has also been demonstrated that erythropoietin does not stimulate tumor proliferation. Increased TE risk associated with ESAs is probably a consequence of increased blood viscosity due to excessive RBC mass elevation with concomitant plasma volume contraction, nitric oxide scavenging, and endothelial cell activation. Increased ESA dosing may also impact survival negatively because EPO contracts the plasma volume and stimulates inflammatory cytokine production independently of increasing erythropoiesis. Furthermore, transfusions themselves are associated with an increase in TE and plasma volume contraction, and these events are potentiated when ESAs are given with transfusions. An update on the management of anemia in oncology, the potential adverse events of ESAs, the benefits and risks of transfusions, and QoL are discussed in this paper. The

show abstract

Section: Recombinant Human Epomentioning

confidence: 99%

Anemia Management in Oncology and Hematology

2009

View full text Add to dashboard Cite

show abstract

“…The sialic acid-containing carbohydrate of erythropoietin determines its serum half-life (Egrie et al, 1993), and darbepoetin alpha has demonstrated a two-to three-fold longer serum half-life than rHuEPO in animal models and in patients with chronic renal failure (MacDougall et al, 1999;Egrie and Browne, 2001). In cancer patients undergoing chemotherapy, darbepoetin alpha therapy increased haemoglobin concentration when administered weekly (QW), or every 2 (Q2W), 3 (Q3W), or 4 (Q4W) weeks (Hedenus et al, 2002;Kotasek et al, 2002;Glaspy et al, 2002).…”

mentioning

confidence: 99%

A dose- and schedule-finding study of darbepoetin alpha for the treatment of chronic anaemia of cancer

Smith

Tchekmedyian²,

Chan

et al. 2003

Br J Cancer

Self Cite

View full text Add to dashboard Cite

A multicentre study evaluated the efficacy and safety of darbepoetin alpha administered weekly (QW), every 3 weeks (Q3W), and every 4 weeks (Q4W) to anaemic patients with cancer not concurrently receiving chemotherapy or radiotherapy. The QW portion (n ¼ 102) was an open-label, sequential, dose-escalation design; cohorts received darbepoetin alpha QW by subcutaneous (s.c.) injection at 0.5, 1.0, 2.25, or 4.5 mg kg À1 week À1 for 12 weeks. The 12-week placebo-controlled, double -blind Q3W (6.75 mg kg À1 ) and Q4W (6.75 or 10.0 mg kg À1 ) schedules (n ¼ 86), which enrolled different patients, took place after the QW schedule and were followed by a 12-week, open-label phase. Patients were evaluated for change in haemoglobin end points and red blood cell transfusions, serum darbepoetin alpha concentration, and safety. Selected domains of health-related quality of life (HRQOL) were measured. With QW dosing, at least 70% of each cohort had a haemoglobin increase from baseline of X2 g dl À1 or a concentration X12 g dl À1 (haematopoietic response). In the 4.5 mg kg À1 QW cohort, all patients achieved a haematopoietic response (100%; 95% confidence interval (CI) ¼ 100, 100). In the Q3W and Q4W schedules, all cohorts had at least 60% of patients who achieved a haematopoietic response. Darbepoetin alpha effectively increases haemoglobin concentration when given QW, Q3W, or Q4W. Less-frequent administration may benefit patients with chronic anaemia of cancer and their caregivers alike.

show abstract

“…Epoetin alfa (Eprex; Ortho Biotech, Toronto, Canada) and darbepoetin alfa (Aranesp; Amgen Inc., Thousand Oaks, CA) are approved in Canada for the treatment of anemia in nonmyeloid malignancies where anemia is a result of the concomitant administration of chemotherapy. Darbepoetin alfa is a recombinant erythropoietin with a longer half-life than epoetin alfa [9], which allows for less frequent dosing with similar efficacy in terms of hemoglobin (Hb) and QoL responses [4, 10,11].…”

Section: Introductionmentioning

confidence: 99%

Effects of Aerobic Exercise Training in Anemic Cancer Patients Receiving Darbepoetin Alfa: A Randomized Controlled Trial

et al. 2008

View full text Add to dashboard Cite

Background. Anemia in patients with solid tumors is a common problem that is associated with impaired exercise capacity, increased fatigue, and lower quality of life (QoL). Erythropoiesis-stimulating agents (ESAs) have been shown to improve these outcomes; however, it is unknown if additional benefits can be achieved with aerobic exercise training.Methods. We conducted a single-center, prospective, randomized, controlled trial in 55 mild-to-moderately anemic patients with solid tumors. Patients were randomized to either darbepoetin alfa alone (DAL, n ‫؍‬ 29) or darbepoetin alfa plus aerobic exercise training (DEX; n ‫؍‬ 26). The DEX group performed aerobic exercise training three times per week at 60%-100% of baseline exercise capacity for 12 weeks. The primary endpoint was QoL assessed by the Functional Assessment of Cancer Therapy-Anemia scale. Secondary endpoints were fatigue, cardio-

show abstract

Darbepoetin alfa given every 1 or 2 weeks alleviates anaemia associated with cancer chemotherapy

Cited by 162 publications

References 14 publications

Anemia Management in Oncology and Hematology

Anemia Management in Oncology and Hematology

A dose- and schedule-finding study of darbepoetin alpha for the treatment of chronic anaemia of cancer

Effects of Aerobic Exercise Training in Anemic Cancer Patients Receiving Darbepoetin Alfa: A Randomized Controlled Trial

Contact Info

Product

Resources

About