Economic Burden of Haematological Adverse Effects in Cancer Patients: A Systematic Review

S.Y. Liou; J.M. Stephens; K.T. Carpiuc; W. Feng; M.F. Botteman; J.W. Hay


Clin Drug Invest. 2007;27(6):381-396. 

In This Article

Abstract and Introduction


Objective: Patients receiving cancer treatments commonly experience haematological adverse effects (AEs) related to chemotherapy or molecularly targeted therapies, which may be associated with high healthcare costs. The objective of this review was to summarize the published literature on the economic burden of neutropenia, thrombocytopenia and anaemia as AEs of cancer treatment.
Methods: A systematic search of the medical literature published between 1990 and 2006 was conducted using PubMed/MEDLINE, EMBASE, BIOSIS, related article links and supplemental searches. References selected for inclusion were prospective or retrospective studies specifically designed to examine the burden of illness, direct medical costs, indirect costs and/or cost drivers associated with neutropenia, thrombocytopenia and anaemia in adult cancer patients. All costs are reported as originally published and adjusted to 2006 US dollars.
Results: In the US, the cost of neutropenia ranged from $US1893 (2006 value $US2632) per outpatient episode to $US38583 ($US49917) per febrile neutropenia hospitalisation. For countries outside the US, the cost of neutropenia appeared to be lower. The cost of thrombocytopenia ranged from $US1035 ($US1395) to $US5328 ($US7635) per cycle or episode in the US. Costs attributable to anaemia ranged from $US18418 ($US22775) to $US69478 ($US93454) per year in the US. The costs of AEs for patients with haematological malignancies appeared to be up to 2–3 times higher than those for patients with solid tumours. Economic studies of the cost of haematological AEs specific to new molecularly targeted treatments for haematological malignancy have not been published.
Conclusions: Chemotherapy-related haematological AEs result in a substantial economic burden on patients, payers, caregivers and society in general. Because of their burden, the frequency and severity of these toxicities should be one of the key factors in the selection of optimal treatments for patients with cancer, especially those with haematological malignancies. Future research is needed to assess the economic burden of AEs associated with new molecularly targeted treatments for haematological malignancies.

1. Introduction

Neutropenia, thrombocytopenia and anaemia are the most frequent haematological complications of cancer treatments. These adverse effects (AEs) contribute to the morbidity, mortality and high healthcare costs associated with cancer and its treatments. In some cases, toxicities can also lead to treatment delays, dose reductions and/or therapy discontinuation, potentially jeopardizing patient treatment outcomes.

Neutropenia, one of the most severe chemotherapy-related AEs, occurs when a myelosuppressive chemotherapy agent reduces absolute neutrophil counts, placing patients at risk for potentially life-threatening infections. Episodes of neutropenia typically last 7-10 days, depending on the chemotherapy regimen, cancer type, presence of co-morbidities and age.[1] Neutropenia is often treated using empirical antibacterials. The frequency and severity of chemotherapy-induced neutropenia can be reduced through prophylactic use of granulocyte colony-stimulating factors (G-CSF).[2] Febrile neutropenia, which is characterized by fever and low absolute neutrophil count, often requires immediate hospitalisation and intensive treatment because of the risk of death from rapidly spreading infection.

Approximately 7-22% of cancer patients who are treated with chemotherapy require hospitalisation for neutropenia.[3,4,5,6] Caggiano et al.[1] estimated that the national incidence rate of neutropenia hospitalisation is 7.83 cases per 1000 cancer patients. Among various cancer types, haematological malignancies have the highest projected rate of neutropenia hospitalisation at 43.3 cases per 1000 patients. Of patients with haematological malignancies, those with leukaemia have the highest estimated incidence of neutropenia hospitalisation at 84.5 cases per 1000 patients.[1]

Prolonged or severe thrombocytopenia (i.e. reduced platelet count) may also be caused by mye-losuppressive chemotherapy, and increases the risk of haemorrhage. Clinically significant bleeding due to chemotherapy-induced thrombocytopenia occurs in <10% of patients with solid tumours.[7] However, thrombocytopenia-related costs can be substantial even in cases without bleeding complications because of the costs of prophylactic platelet transfusions, routine blood tests and clinic visits. Chemotherapy-induced thrombocytopenia may be managed by platelet transfusions, platelet growth factors such as recombinant human interleukin-11, delays in subsequent cycles of treatment, or chemotherapy dose reductions.

Anaemia is characterized by decreased red blood cell (RBC) count and is usually measured by a decrease in haemoglobin. Symptoms of anaemia include fatigue, lethargy, tiredness or lack of energy. Chemotherapy induces anaemia by inhibiting RBC production, erythroid cell maturation and synthesis of erythropoietin by the kidneys.[8] Chemotherapy-induced anaemia is traditionally treated with RBC transfusions. Erythropoietic agents (e.g. epoetin alfa and darbepoetin alfa) that stimulate RBC production are another option, although these agents are more expensive.

The incidence of grade 3 or 4 chemotherapy-induced anaemia can be as high as 80%, although the rate varies significantly depending on the cancer type and chemotherapy regimen administered. Furthermore, the incidence of anaemia tends to increase over the course of chemotherapy.[9] The odds of having anaemia are 4.5 times higher in patients with haematological malignancies than in patients with other tumour types.[10]

A recently conducted population-based study of chemotherapy-related serious adverse events (defined as those that result in death or significant disability, require hospital admission or prolongation of an existing hospital stay, or are life-threatening) in younger breast cancer patients found that chemotherapy-related serious AEs may be more common and lead to higher healthcare expenditures than previously estimated.[11] In terms of serious haematological AEs, patients who received chemotherapy had 14.6-fold greater odds of experiencing neutropenia or thrombocytopenia and 3.0-fold greater odds of experiencing anaemia compared with those who did not receive chemotherapy. Furthermore, patients with chemotherapy-related serious AEs (both haematological and non-haematological) had large incremental expenditures for hospitalisations and emergency room visits (2006 value $US13313 per person per year) and ambulatory encounters (2006 value $US16021 per person per year). These data emphasize the importance of considering the common AEs of chemotherapy and their associated costs in addition to clinical effectiveness when determining which treatments are likely to benefit patients the most.

Advances in the management of haematological malignancies include molecularly targeted treatments such as imatinib and dasatinib, together with others in late-phase development including nilotinib. The value of these targeted therapies lies in their superior efficacy, survival and safety compared with traditional chemotherapies. However, differences in clinical profiles (particularly adverse effect profiles) of these targeted therapies may have implications for the cost of care. Understanding the potential burden associated with haematological AEs relative to both conventional chemotherapies and targeted therapies is of particular interest in the management of haematological malignancies. For example, the incidence of grade 3/4 haematological AEs may be as high as 70-80% in resistant chronic myelogenous leukaemia patients with advanced disease receiving targeted treatments.[12] Rates of haematological AEs with targeted therapies may vary by agent, and thus an understanding of the potential cost impact for each of these AEs would be helpful to decision makers evaluating the efficacy and safety of the various treatment options. Because these targeted treatments are relatively new and thorough economic analyses of the burden of their AEs have not yet been conducted, a potential starting point for understanding the costs of haematological AEs for targeted cancer treatments would be to summarize what is known about the costs of these AEs for traditional chemotherapy. Therefore, the purpose of this review was to summarize and discuss (i) the published literature documenting the costs of neutropenia, thrombocytopenia and anaemia in adult cancer patients receiving either targeted therapies or chemotherapy, and (ii) the drivers of these costs. Of particular interest were any differences in AE costs between patients with haematological malignancies and those with solid tumours.


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