Anaemia in cancer: pathophysiology and treatment

Mercadante, Sebastiano; Gebbia, Vittorio; Marrazzo, Antonio; Filosto, Simone

doi:10.1053/ctrv.2000.0181

Cited by 188 publications

(147 citation statements)

References 34 publications

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“…Cost Red blood cell transfusions have historically been viewed as less expensive than rHuEPO (Ludwig and Fritz, 1998a;Mercadante et al, 2000). It is difficult, however, to gain a current, accurate measurement of the cost of acquiring, handling, processing, storing and administering blood; the costs associated with the complications of transfusions; and the indirect economic costs to patients due to travelling to a transfusion centre and/or absence from work.…”

Section: Inadequacies In the Current Treatment Optionsmentioning

confidence: 99%

“…Outstanding issues Further studies using rHuEPO are needed to address additional issues such as the optimal dose and schedule (Glaspy et al, 1997), when to stop the drug because of lack of response, and when to increase the dose (Mercadante et al, 2000). It has been suggested that an initial dose of rHuEPO of 150 U kg -1 is given three times weekly subcutaneously, which is increased to 300 U kg -1 if the haemoglobin value does not increase by ≥ 1 g dl -1 after 4 weeks of therapy.…”

Section: Inadequacies In the Current Treatment Optionsmentioning

confidence: 99%

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Anaemia and its functional consequences in cancer patients: current challenges in management and prospects for improving therapy

Demetri

2001

Br J Cancer

100

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Anaemia is a common occurrence in patients with cancer and contributes to the clinical symptomatology and reduced quality of life (QOL) seen in cancer patients. Many aspects of reduced QOL, including fatigue, are known to be associated with suboptimally low levels of haemoglobin. Even mild-to-moderate anaemia adversely affects patient-reported QOL parameters. Red blood cell transfusions are associated with many real and perceived risks, inconveniences, costs, and only temporary benefits. Recombinant human erythropoietin (rHuEPO) is an effective therapy to increase haemoglobin values in over half of anaemic cancer patients receiving concurrent chemotherapy. These increased haemoglobin values are closely correlated with improvements in QOL. Despite these objectively defined benefits, less than 50% of anaemic patients undergoing cytotoxic chemotherapy receive rHuEPO, in contrast to patients with chronic renal failure on dialysis, where anaemia is universally and aggressively treated to more optimal haemoglobin values. However, there are several barriers that may limit more widespread use of rHuEPO. These include inconvenience associated with frequent dosing; failure of a large proportion (40 to 50%) of patients to respond; relatively slow time to response; absence of reliable early indicators of response; and current lack of rigorous pharmacoeconomic data demonstrating cost-effectiveness. Darbepoetin alfa is a novel erythropoiesis stimulating protein (NESP) that is biochemically distinct from rHuEPO, and which has been proven to stimulate red blood cell production. The molecule has a 3-fold longer half-life and increased biological activity that will allow less frequent dosing, facilitating improved management of the anaemia of cancer. With this new option for therapy, further avenues of investigation should lead to renewed interest in the clinical benefits of optimal haemoglobin levels for patients with cancer. © 2001 Cance Cancer Research Campaign

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Section: Inadequacies In the Current Treatment Optionsmentioning

confidence: 99%

Section: Inadequacies In the Current Treatment Optionsmentioning

confidence: 99%

Anaemia and its functional consequences in cancer patients: current challenges in management and prospects for improving therapy

Demetri

2001

Br J Cancer

100

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“…Anaemia in cancer patients results from a complex combination of factors including processes resulting from both the disease itself and from its treatment (Spivak, 1994;Mercadante et al, 2000). The control of anaemia in cancer patients is important not only for the immediate well-being of the patient but may also be linked to treatment outcome (Tarnawski et al, 1997;Lee et al, 1998;Warde et al, 1998;Canaday et al, 1999;Grogan et al, 1999;Obermair et al, 2000;Phan et al, 2001;Pangalis et al, 2002).…”

mentioning

confidence: 99%

Kinetics of haematopoietic recovery after dose‐intensive chemo/radiotherapy in mice: optimized erythroid support with darbepoetin alpha

et al. 2003

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Summary. Despite its frequency and impact on clinical outcomes, anaemia in cancer patients remains poorly understood and suboptimally treated. The definition of optimum treatment schedules with erythropoietic agents requires a suitable model of chemotherapy-induced progressive anaemia. This study investigated novel strategies such as once-per-chemotherapy-cycle dosing, synchronization between erythroid supportive care and chemotherapy, and definition of the optimum timing of erythroid support. A murine model of carboplatin chemotherapy/radiotherapy (CRT)-induced anaemia was used, which caused progressive anaemia across multiple cycles. Weekly administration of recombinant human erythropoietin (rHuEPO) was effective, but the longer-acting darbepoetin alpha resulted in superior responses. In all animals, anaemia became progressive and more refractory across cycles because of accumulated bone marrow damage. Exploiting a specific enzyme-linked immunosorbent assay, which could distinguish between darbepoetin alpha and endogenous erythropoietin, the effect of CRT upon the pharmacokinetics of darbepoetin alpha showed that clearance of darbepoetin alpha, and presumably erythropoietin, was at least partially dependent on a chemotherapy-sensitive pathway. Scheduling data suggested that administration of erythropoietic agents prior to chemotherapy was more effective than administration after chemotherapy. There was no evidence that erythropoietic agents exacerbated anaemia, even when administered immediately prior to CRT in an attempt to 'prime' erythroid cells for the effects of CRT.

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“…Intensive sequential HD-chemotherapy is associated with the risk of severe neutropenia, thrombocytopenia and anaemia despite the use of PBSC retransplantation and haemato-poetic growth factors (granulocyte colony stimulating factor) (G-CSF). There is an increasing awareness among the oncology community that the decrease of haemoglobin (Hb) concentrations may lead to physical and psychological consequences that adversely effect the quality of life of cancer patients (Eguchi, 1995;Thatcher, 1998;Groopman and Itri, 1999;Ray-Coquard et al, 1999;BarrettLee et al, 2000;Mercadante et al, 2000;Littlewood et al, 2001).…”

mentioning

confidence: 99%

“…RBC transfusions may be associated with adverse effects such as viral infections, e.g. hepatitis and HIV, bacterial and parasitic infections, haemolysis and immunologic or anaphylactic reactions (Eguchi, 1995;Thatcher, 1998;Groopman and Itri, 1999;Ray-Coquard et al, 1999;Mercadante et al, 2000).…”

mentioning

confidence: 99%

Treatment-induced anaemia and its potential clinical impact in patients receiving sequential high dose chemotherapy for metastatic testicular cancer

et al. 2002

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First-line sequential high dose chemotherapy is under investigation in patients with 'poor prognosis' metastatic germ cell tumours in order to improve survival. Despite the use of autologous peripheral blood stem cell transplantation and granulocyte colony stimulating factor chemotherapy dose intensification is associated with severe haematotoxicity including anaemia, which may significantly affect quality of life and tolerability of chemotherapy. This study investigates the frequency and degree of anaemia in patients receiving first-line sequential high dose chemotherapy for metastatic testicular cancer and the impact of anaemia on treatment outcome. A total of 101 newly diagnosed patients with 'poor prognosis' metastatic nonseminomatous germ cell tumours were treated with one cycle of standard VIP followed by three cycles of HD-VIPchemotherapy (etoposide, ifosfamide, cisplatin) within a large phase I/II study. Differential blood cell counts were taken prior, during and after every cycle of chemotherapy. Additionally, the numbers of red blood cell and platelet transfusions were recorded. Kaplan -Meier analyses were performed to correlate pre-treatment and post-treatment haemoglobin values to response and overall survival. Forty-eight per cent of the patients were classified anaemic (haemoglobin 512 g dl 71 ) prior to the start of chemotherapy. The application of sequential HD-VIP resulted in median haemoglobin nadirs between 7.8 g dl 71 (range 5.5 -11.1 g dl 71 ) in the first cycle and 7.6 g dl 71 (range 6.0 -11.4 g dl 71 ) in the third cycle despite the frequent use of red blood cell transfusions. Almost all patients (99%) had haemoglobin levels 510 g dl 71 at some timepoint during first-line sequential high dose chemotherapy. Overall, 97 patients received red blood cell transfusions with a median of 10 units (range 2 -25) per patient during the four consecutive cycles of therapy. The time to first transfusion was shortest in patients with the lowest initial haemoglobin values. While there was no prediction of response or outcome by baseline haemoglobin-levels, a significant survival difference in favour of patients with a haemoglobin value 410.5 g dl 71 after completion of four cycles of therapy (at leukocyte recovery after the last cycle) compared to those with haemoglobin values 510.5 g dl 71 was found with 3-year overall survival rates of 87% vs 68%, respectively (P50.05). Severe anaemia is a very frequent side effect of sequential dose intensive therapy in patients with germ cell cancer, with almost all patients becoming transfusion dependent. Despite the frequent use of red blood cell transfusions, median haemoglobin nadirs remained about 7.5 -8 g dl 71 during therapy. A correlation of haemoglobin-values after completion of therapy to overall treatment outcome was found.

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Anaemia in cancer: pathophysiology and treatment

Cited by 188 publications

References 34 publications

Anaemia and its functional consequences in cancer patients: current challenges in management and prospects for improving therapy

Anaemia and its functional consequences in cancer patients: current challenges in management and prospects for improving therapy

Kinetics of haematopoietic recovery after dose‐intensive chemo/radiotherapy in mice: optimized erythroid support with darbepoetin alpha

Treatment-induced anaemia and its potential clinical impact in patients receiving sequential high dose chemotherapy for metastatic testicular cancer

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