Review articleAnaemia in elderly patients with cancer: Focus on chemotherapy-induced anaemia
Introduction
The term “elderly” has, in recent publications, ranged from ≥ 65 years to ≥ 80 years of age,1 with the most often used age split being 65 or 70 years. The International Society of Geriatric Oncology (SIOG) defines “elderly” as ≥ 75 years of age. This is felt to more accurately represent an age that is associated with an increased risk of cancer and other comorbidities.2 As health care standards and life expectancy are increasing in the developed world, chronological and biological ages are diverging. The use of a Comprehensive Geriatric Assessment (CGA), including biological and clinical markers, is recommended for elderly patients with cancer.3 This assessment makes it possible to evaluate the stage of aging and to determine individual unaddressed problems in this population.3
As such, the ≥ 65 years age group is the most rapidly increasing section of the population.1 However, elderly patients (patients ≥ 65 years of age) are often underrepresented in clinical studies. An analysis was conducted on data from 59,300 patients with cancer in phase II or III trials. This revealed that only 32% of the patients in these trials were ≥ 65 years of age, despite this population accounting for about 61% of patients with cancer in the USA.4 Furthermore, it is predicted that, by 2050, 80% of all cancers will occur in this population due to progressing demographic changes.5
The development of anaemia is frequently associated with cancer. The European Cancer Anaemia Survey examined the prevalence of anaemia in a cohort of 15,367 patients with cancer, with no specific age groups (18–96 years). In this survey, anaemia was defined as having a haemoglobin (Hb) level < 12 g/dL due to any cause. Data from the survey revealed a prevalence of 39.3% at enrollment, peaking at 67.0% during the course of the survey.6
The cause of anaemia is multifactorial. In individuals without cancer, particularly the elderly, anaemia may be caused by factors such as chronic renal disease; chronic inflammation; iron, folate, or B12 deficiencies; or be unexplained.7 While these remain potential causes of anaemia in patients with cancer, two further etiologies/types of anaemia are specific to these patients. Firstly, cancer-related anaemia (CRA), also referred to as anaemia of cancer, is a type of anaemia of chronic disease which occurs due to chronic immune activation stemming from the patients' disease.8 The other type of anaemia occurring in patients with cancer is chemotherapy-induced anaemia (CIA). CIA develops as a result of the effects of some chemotherapeutic treatments. It has been noted that some chemotherapeutic treatments carry more of a risk of developing CIA than others. In particular, treatment with platinum-based therapies carries a high risk of inducing CIA.9 Of course, the anaemia seen in patients with cancer may be a result of both CIA and CRA combined.
Three of the most common therapies for the treatment of CIA are red blood cell (RBC) transfusions, iron supplementation (where iron deficiency has been diagnosed), and erythropoiesis-stimulating agents (ESAs). However, the ability of elderly patients to tolerate additional therapy while receiving chemotherapy may be attenuated, due to their biological age and comorbidities, when compared with younger patients. As we begin to uncover the specific needs of this population of patients with cancer, it is important to understand whether the currently available treatment modalities are still appropriate.
In this article, we consider the impact of CIA in the elderly, and explore current evidence in elderly patients for the use of RBC transfusions, iron supplementation, and ESA for the treatment of CIA.
Section snippets
Impact of anaemia (including CIA) in the elderly
Anaemia effects functional capacity, quality of life (QoL), mood, and cognitive function.
Lucca et al. examined cognition and functioning in 170 mildly anaemic and 547 non-anaemic persons aged 65–84 years. This study revealed that mildly anaemic elderly individuals had significantly worse results on almost all cognitive, functional, mood, and QoL measures than the non-anaemic persons. Mild anaemia was therefore independently associated with worse selective attention performance and
Chemotherapy and the risk of anaemia in elderly patients with cancer
Decline in organ function can alter the pharmacokinetics of chemotherapies used in elderly patients. Therefore, elderly patients with cancer are at greater risk of experiencing chemotherapy toxicity than younger patients.21 Additionally, there is a significant increase in the occurrence of comorbidities in elderly patients compared to younger patients. It has been shown that elderly people (≥ 65 years of age) have an average of three chronic comorbidities.[22], [23] These can increase the risk of
Treatment of CIA in elderly patients with cancer
Recommendations by the American Society of Clinical Oncology (ASCO) and American Society of Hematology (ASH) state that anaemia, and in particular CIA, should be treated in elderly patients with cancer.[21], [27] Despite this, often the treatment of anaemia in elderly patients with cancer is not perceived as a high priority by oncologists9; this may explain the high proportion (60%) of patients with cancer (independent of age) in which anaemia remains untreated.28 Indeed, while severe anaemia
Summary
In summary, from the data presented in this review, the studies suggest that elderly patients with CIA experience substantial benefit from anaemia management, showing increased Hb level and improved QoL. Benefits from CIA treatment are observed in many aspects of elderly patients' lives, including cognition, fatigue, and functional capacity. Clinicians should be aware of these benefits, and, as data availability increases, the benefits of treating CIA in elderly patients with cancer may become
Author contributions
All authors have participated in the preparation of the manuscript and have approved the final version.
Disclosures and Conflict of Interest Statements
The authors disclose the following conflict of interest within the past 3 years:
HL: Honoraria for lectures from Celgene, Ortho-Biotech, and Mundipharma; research funding from Ortho-Biotech, Celgene, and Mundipharma
UW: Research support—Janssen-Cilag; Speakers Honorary—Novartis, Ortho-Biothec, Roche, Amgen, Cephalon, Pro-Starkan.
SVB: Consultant for Amgen Belgium
Acknowledgements
We would like to thank the people who helped in the preparation of this manuscript, in particular Archimed Medical Communication AG for their writing support (funded by Amgen [Europe] GmbH).
References (74)
- et al.
Treatment of the elderly colorectal cancer patient: SIOG expert recommendations
Ann Oncol
(2009) - et al.
The illness trajectory of elderly cancer patients across cultures: SIOG position paper
Ann Oncol
(2007) - et al.
Use of comprehensive geriatric assessment in older cancer patients: recommendations from the task force on CGA of the International Society of Geriatric Oncology (SIOG)
Crit Rev Oncol Hematol
(2005) - et al.
The European Cancer Anaemia Survey (ECAS): a large, multinational, prospective survey defining the prevalence, incidence, and treatment of anaemia in cancer patients
Eur J Cancer
(2004) - et al.
Prevalence of anemia in persons 65 years and older in the United States: evidence for a high rate of unexplained anemia
Blood
(2004) Impact of fatigue on quality of life in oncology patients
Semin Hematol
(2000)- et al.
Mild anemia and the risk of falls in older adults from nursing homes and the community
J Am Med Dir Assoc
(2004) - et al.
Correlation between anemia and functional/cognitive capacity in elderly lung cancer patients treated with chemotherapy
Ann Oncol
(2006) - et al.
Association of comorbidity with disability in older women: the Women's Health and Aging Study
J Clin Epidemiol
(1999) - et al.
Chemotherapy-associated toxicity in a large cohort of elderly patients with non-small cell lung cancer
J Thorac Oncol
(2010)
Advanced ovarian cancer in the elderly: results of consecutive trials with cisplatin-based chemotherapy
Crit Rev Oncol Hematol
Incidence and clinical impact of chemotherapy induced myelotoxicity in cancer patients: an observational retrospective survey
Crit Rev Oncol Hematol
Age, anemia, and fatigue
Semin Oncol
The hazards of blood transfusion in historical perspective
Blood
Transfusion and lung injury
Transfus Clin Biol
Aging of the immune system: how much can the adaptive immune system adapt?
Immunity
Use of epoetin and darbepoetin in patients with cancer: 2007 American Society of Hematology/American Society of Clinical Oncology clinical practice guideline update
Blood
Blood transfusion reduction with intravenous iron in gynecologic cancer patients receiving chemotherapy
Gynecol Oncol
EORTC guidelines for the use of erythropoietic proteins in anaemic patients with cancer: 2006 update
Eur J Cancer
Effect of age on hemoglobin levels and quality of life following treatment with epoetin alfa in cancer patients
Crit Rev Oncol Hematol
Evaluation of the effectiveness of treatment with erythropoietin on anemia, cognitive functioning and functions studied by comprehensive geriatric assessment in elderly cancer patients with anemia related to cancer chemotherapy
Crit Rev Oncol Hematol
Recombinant human erythropoiesis-stimulating agents and mortality in patients with cancer: a meta-analysis of randomised trials
Lancet
Use of growth factors in the elderly patient with cancer: a report from the Second International Society for Geriatric Oncology (SIOG) 2001 meeting
Crit Rev Oncol Hematol
Fixed-dose rate gemcitabine in elderly patients with advanced pancreatic cancer: an observational study
Crit Rev Oncol Hematol
Single-agent pemetrexed or sequential pemetrexed/gemcitabine as front-line treatment of advanced non-small cell lung cancer in elderly patients or patients ineligible for platinum-based chemotherapy: a multicenter, randomized, phase II trial
J Thorac Oncol
Second-line chemotherapy with a modified schedule of docetaxel in elderly patients with advanced-stage non-small-cell lung cancer
Clin Lung Cancer
Raltitrexed plus levofolinic acid and bolus/continuous infusion 5-fluorouracil on a biweekly schedule for elderly patients with advanced colorectal carcinomas
Ann Oncol
Increased dose-intensity of gemcitabine in advanced non small cell lung cancer (NSCLC): a multicenter phase II study in elderly patients from the “polmone toscano group” (POLTO)
Lung Cancer
Gemcitabine and low dose carboplatin in the treatment of elderly patients with advanced non-small cell lung cancer
Lung Cancer
Activity and toxicity of gemcitabine and gemcitabine + vinorelbine in advanced non-small-cell lung cancer elderly patients: Phase II data from the Multicenter Italian Lung Cancer in the Elderly Study (MILES) randomized trial
Lung Cancer
Gemcitabine monotherapy in elderly patients with advanced non-small cell lung cancer: a multicenter phase II study
Lung Cancer
Participation of patients 65 years of age or older in cancer clinical trials
J Clin Oncol
Anemia, cancer, and aging
Cancer Control
Cancer-related anemia: pathogenesis, prevalence and treatment
Oncology
Chemotherapy-induced anemia in adults: incidence and treatment
J Natl Cancer Inst
Association of mild anemia with cognitive, functional, mood and quality of life outcomes in the elderly: the “Health and Anemia” study
PLoS One
Anaemia-related impairment in quality of life in elderly cancer patients prior to chemotherapy
J Cancer Res Clin Oncol
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