Management of cancer in the older person: a practical approach

The management of cancer in the older aged person is an increasingly common problem. The questions arising from this problem are: Is the patient going to die with cancer or of cancer? Is the patient able to tolerate the stress of antineoplastic therapy? Is the treatment producing more benefits than harm? This article explores a practical, albeit evolving, approach to these questions including a multidimensional assessment of the older person and simple pharmacologic interventions that may ameliorate the toxicity of antineoplastic agents. Age may be construed as a progressive loss of stress tolerance, due to decline in functional reserve of multiple organ systems, high prevalence of comorbid conditions, limited socioeconomic support, reduced cognition, and higher prevalence of depression. Aging is highly individualized: chronologic age may not reflect the functional reserve and life expectancy of an individual. A comprehensive geriatric assessment (CGA) best accounts for the diversities in the geriatric population. The advantages of the CGA include:Recognition of potentially treatable conditions such as depression or malnutrition, that may lessen the tolerance of cancer treatment and be reversed with proper intervention; Assessment of individual functional reserve; Gross estimate of individual life expectancy; and Adoption of a common language to classify older cancer patients. The CGA allows the practitioner to recognize at least three stages of aging:People who are functionally independent and without comorbidity, who are candidates for any form of standard cancer treatment, with the possible exception of bone marrow transplant. People who are frail (dependence in one or more activities of daily living, three or more comorbid conditions, one or more geriatric syndromes), who are a candidate only for palliative treatment; and People in between, who may benefit from some special pharmacological approach, such as reduction in the initial dose of chemotherapy with subsequent does escalations. The pharmacological changes of age include decreased renal excretion of drugs and increased susceptibility to myelosuppression, mucositis, cardiotoxicity and neurotoxicity. Based on these findings, the proposal was made that all persons aged 70 and older, treated with cytotoxic chemotherapy of dose intensity comparable to CHOP, receive prophylactic growth factor treatment, and that the hemoglobin of these patients be maintained >/=12 gm/dl.     

Cancer and aging. An evolving panorama

This article illustrates how the nosology of cancer evolves with the patient's age. If the current trends are maintained, 70% of all neoplasms will occur in persons aged 65 years and over by the year 2020, leading to increased cancer-related morbidity among older persons. Cancer control in the older person involves chemoprevention, early diagnosis, and timely and effective treatment that entails both antineoplastic therapy and symptom management. These interventions must be individualized based on a multidimensional assessment that can predict life expectancy and treatment complications and that may evaluate the quality of life of the older person. This article suggests a number of interventions that may improve cancer control in the aged. Public education is needed to illustrate the benefits of health maintenance and early detection of cancer even among older individuals, to create realistic expectations, and to heighten awareness of early symptoms and signs of cancer. Professional education is needed to train students and practitioners in the evaluation and management of the older person. Of special interest is the current initiative of the Hartford Foundation offering combined fellowships in oncology and geriatrics and incorporating principles of geriatric medicine in medical specialty training. Prudent pharmacologic principles must be followed in managing older persons with cytotoxic chemotherapy. These principles include adjusting the dose according to the patient's renal function, using epoietin to maintain hemoglobin levels of 12 g/dL or more, and using hemopoietic growth factors in persons aged 70 years and older receiving cytotoxic chemotherapy of moderate toxicity (e.g., CHOP). To assure uniformity of data, a cooperative oncology group should formulate a geriatric package outlining a common plan for evaluating function and comorbidity. This article also suggests several important areas of research items: Molecular interactions of age and cancer Host-tumor interactions in the older tumor host Chemoprevention of cancer and aging Laboratory evaluation of aging Development of shorter forms of geriatric assessment Management of the frail cancer patients Clinical trials of tumor-specific issues.     

Geriatric oncology: challenges for the new century

The management of cancer in the older aged person represents one of the major immediate challenges of medicine. The response to this challenge involves answers to the following questions: I. Who is old? Currently. 70 years of age may he considered the lower limit of senescence because the majority of age-related changes occur after this age. Individual estimates of life expectancy and functional reserve may be obtained by a comprehensive and time-consuming multidimensional geriatric assessment. The current instrument may be fine-tuned and new instruments, including laboratory tests of ageing. may be developed. 2. Why do older persons develop more cancer? It is clear that ageing tissues are more susceptible to late-stage carcinogen. Older persons may represent a natural monitor system for new environmental carcinogens, and may also represent a fruitful ground to study the late stages of carcinogenesis. 3. Is cancer different in younger and older persons? Clearly. the behaviour of some tumors. including acute myeloid leukaemia, non-Hodgkin's lymphoma and breast cancer change with the age of the patient. The mechanisms of these changes that may involve both the tumour cell and the tumour host are poorly understood. 4. Can cancer he prevented in older individuals? Chemoprevention offers a new horizon of possibilities for cancer prevention: older persons may benefit most from chemoprevention due to increased susceptibility to environmental carcinogens. Screening tests may become more accurate in older individuals due to increased prevalence of cancer. hut may he less beneficial due to more limited patient life expectancy. 5. Do older persons benefit from cytotoxic treatment? The answer to this question partly stands on proper patient selection. partly on the development of safer forms of cancer treatment and prudent use of antidotes to chemotherapy toxicity. 6. What is the cost of treating older cancer patients? The treatment of older patients is generally more costly. This cost should be assessed against the cost of not treating cancer and promoting functional dependence. which by itself is extremely costly. 7. What are the endpoints of clinical trials in older cancer patients? With more limited life expectancy. the effect of treatment on quality of life is paramount. Reliable assessment of quality of life is essential for interpreting clinical trials in older individuals. 2000 Elsevier Science Ltd. All rights reserved.     

Clinical tools for chemotherapy toxicity prediction and survival in geriatric cancer patients

Chemotherapy is one of the main treatments for cancer and is associated in many cancers with significant benefits in overall and disease-free survival. Nevertheless, it is also associated with adverse effects that make its administration difficult in patients with comorbidities or decreased general status. Older patients belong more often to these categories because of the physiologic effects of aging in organ functions but also because of longer effects of chronic conditions in different organs. As a result, the decision for administration of possibly beneficial chemotherapy to older patients becomes more problematic given that there is a requirement to balance this benefit with a higher probability of severe adverse effects that may even culminate to patient’s demise. Thus, the ability to predict accurately the subset of older patients that will develop severe adverse effects with chemotherapy and, conversely, those that will tolerate it with a more acceptable adverse effect profile, is of clinical importance. This article will discuss progress made in devising predictive tools for use in older patients with cancer considered for receiving chemotherapy. A discussion of recent developments on the related but distinct subject of prediction of mortality in geriatric cancer patients with a focus on those receiving chemotherapy will also be included to provide a data-frame of the status of survival prediction tools in geriatric oncology patients.     

Evaluating the Older Patient with Cancer: Understanding Frailty and the Geriatric Assessment

The majority of cancer incidence and mortality occurs in individuals aged older than 65 years, and the number of older adults with cancer is projected to significantly increase secondary to the aging of the US population. As such, understanding the changes accompanying age in the context of the cancer patient is of critical importance. Age‐related changes can impact tolerance of anticancer therapy and can shift the overall risk‐benefit ratio of such treatment. A challenge in implementing evidence‐based approaches in older adults is the under–representation of this group in oncology clinical trials. In addition, although older adults are particularly vulnerable to the side effects of cancer therapy, few oncology studies to date have incorporated a measure of health status other than the Eastern Cooperative Oncology Group or Karnofsky performance scales. Novel metrics such as frailty indices or the geriatric assessment recognize heterogeneity among older adults, and may allow for risk‐adapted approaches to therapy. It is increasingly recognized that several laboratory markers may predict morbidity and mortality in older adults; these biologic variables may further aid in stratifying this group of patients based on risk. This review describes key studies from the geriatric literature that provide principles for assessing health status in the older patient, and ways that these principles can be applied to oncology care in an older population are proposed. CA Cancer J Clin 2010;60:120–132. © 2010 American Cancer Society, Inc.     

Adjuvant Chemotherapy for Breast Cancer in Older Women: Emerging Evidence to Aid in Decision Making

To prevent breast cancer-related recurrence and death, adjuvant therapy, including chemotherapy, is given. The decision to deliver chemotherapy requires careful weighing of the risk of toxicity versus the estimated benefit. The risk and benefit are based on information from clinical trials, statistical models, and past clinical experience . Compared to younger patients, it is perceived that older patients have cancers that are lower risk, gain less benefit from chemotherapy, and are at higher risk of toxicity. There is now strong evidence that healthy older women tolerate treatment and stand to gain the same benefits from treatment as do younger women. Numeric age alone, therefore, does not justify withholding adjuvant chemotherapy. New tools to aid in the decision are needed. Fortunately, the expected great increase in the size of the geriatric population spawned the field of geriatric oncology and the development of brief, practical versions of the Comprehensive Geriatric Assessment (CGA) for use in busy oncology clinics are in sight. It is time for us to incorporate elements of the CGA into practice, to systematically identify older patients at substantial risk of toxicity. For frail older women with breast cancer, no therapy or less toxic therapies can be considered, some of which are suggested herein. In addition, as always in oncology, physicians and patients should look for and participate in clinical trials that will define how to treat cancer, especially in older patients, in the future.     

Radiothérapie des cancers bronchiques non à petites cellules des sujets âgés

People over the age of 65 are often excluded from participation in oncological clinical trials. However, more than half of patients diagnosed with non-small-cell lung cancer are older than 65 years. Any therapeutic strategy must be discussed in multidisciplinary meetings after adapted geriatric assessment. Patients who benefit from the comprehensive geriatric assessment (CGA) of Balducci and Extermann are those whose G8 screening tool score is less than or equal to 14. Age itself does not contraindicate a curative therapeutic approach. Stereotactic radiotherapy is an alternative to surgery for early stages in elderly patients who are medically inoperable or who refuse surgery, because it significantly increases overall survival. Mostly sequential (rarely concomitant) chemoradiotherapy can be proposed to elderly patients with locally advanced stages in good general state of health. For the others, an exclusive palliative radiotherapy, a single or dual agent of chemotherapy, a targeted drug or best supportive care only may be discussed.     

Tolerance to chemotherapy in elderly patients with cancer.

BACKGROUND: Due to demographic changes, the number of elderly people with cancer will increase in the next decades. In the past, elderly patients with cancer were often excluded from clinical trials. Chronological age has been considered a risk factor for increased toxicity and reduced tolerance to chemotherapy. METHODS: We present a review on toxicity of chemotherapy and factors associated with toxicity in elderly patients with cancer, and we discuss chemotherapeutic agents and treatment options in treating this patient population. RESULTS: Age is a risk factor for increased toxicity to chemotherapy and decreased tolerance. However, few trials have been reported with adjustment for age-associated changes such as impairment of functional status and increased comorbidity, which also show an independent association with increased toxicity. Published data may include several biases, such as referral and publication bias. CONCLUSIONS: Decision making in elderly cancer patients should be based on the results of a geriatric assessment. Patients with few or no limitations should be treated as younger patients are treated. Data with a high level of evidence are unavailable for patients showing moderate or severe limitations in a geriatric assessment.     

General recommendations paper on the management of older patients with cancer: the SEOM geriatric oncology task force’s position statement

Population aging is associated with greater numbers of older people with cancer. Thanks to treatment advances, not only are more seniors diagnosed with cancer, but there are also more and more older cancer survivors. This upward trend will continue. Given the heterogeneity of aging, managing older patients with cancer poses a significant challenge for Medical Oncology. In Spain, a Geriatric Oncology Task Force has been set up within the framework of the Spanish Society for Medical Oncology (SEOM). With the aim of generating evidence and raising awareness, as well as helping medical oncologists in their training with respect to seniors with cancer, we have put together a series of basic management recommendations for this population. Many of the patients who are assessed in routine clinical practice in Oncology are older. CGA is the basic tool by means of which to evaluate older people with cancer and to understand their needs. Training and the correct use of recommendations regarding treatment for comorbidities and geriatric syndromes, support care, and drug–drug interactions and toxicities, including those of antineoplastic agents, as detailed in this article, will ensure that this population is properly managed.     

Use of geriatric assessment in hematopoietic cell transplant

Hematopoietic cell transplant (HCT) is an important aspect of treatment for many hematologic malignancies. As cancer is a disease associated with aging, and hematologic malignancies are no exception, rates of autologous and allogeneic HCT utilization in older adults are on the rise. The most common indications for autologous HCT are multiple myeloma and lymphoma, and for allogenic HCT are acute myeloid leukemia and myelodysplastic syndrome. Older adults into their eighth decade of life can have favorable outcomes after autologous and allogeneic HCT, at least among select patients. Evaluation of older adults prior to HCT can be aided by utilizing a geriatric assessment (GA). GA can identify areas of vulnerability in older adults prior to HCT not captured by more traditional measures. In the future, GA may be utilized to guide interventions prior to HCT to improve outcomes of older adults. Further studies are needed to expand the paucity of data in utilizing GA to identify three groups of patients: those who clearly benefit from HCT, those who would clearly be harmed, and those who might benefit but would require additional support during and after HCT.     

Geriatric assessment for oncologists

The world is experiencing aging of its population. Age-specific incidence rates of cancer are higher and cancer is now recognized as a part of aging. Treating older patients can be challenging. The clinical behavior of some tumors changes with age and the aging process itself brings physiological changes leading to decline in the function of organs. It is essential to identify those patients with longer life expectancy, potentially more likely to benefit from aggressive treatment vs. those that are more vulnerable to adverse outcomes. A primary determination when considering therapy for an older cancer patient is a patient’s physiologic, rather than chronologic age. In order to differentiate amongst patients of the same age, it is useful to determine if a patient is fit or frail. Frail older adults have multiple chronic conditions and difficulties maintaining independence. They may be more vulnerable to therapy toxicities, and may not have substantial lasting benefits from therapy. Geriatric assessment (GA) may be used as a tool to determine reversible deficits and devise treatment strategies to mitigate such deficits. GA is also used in treatment decision making by clinicians, helping to risk stratify patients prior to potentially high-risk therapy. An important practical aspect of GA is the feasibility of incorporating it into a busy oncology practice. Key considerations in performing the GA include: available resources, patient population, GA tools to use, and who will be responsible for using the GA results and develop care plans. Challenges in implementing GA in clinical practice will be discussed.KEYWORDS : Geriatric oncology, geriatric assessment (GA), frailty     

Real-world evidence on adjuvant chemotherapy in older adults with stage II/III colon cancer

Colon cancer represents one of the most common cancers diagnosed in older adults worldwide. The standard of care in resected stage II and stage III colon cancer continues to evolve. While there is unequivocal evidence to suggest both disease free and overall survival benefits with the use of combination chemotherapy in patients with stage III colon cancer, data regarding its use in patients with stage II colon cancer are less clear. Further, although colon cancer is a disease that affects older adults, there is considerable debate on the value of adjuvant chemotherapy in the aging population. In particular, many older patients are undertreated when compared to their younger counterparts. In this review, we will describe the clinical trials that contributed to the current adjuvant chemotherapy approach in colon cancer, discuss representation of older adults in trials and the specific challenges associated with the management of this sub-population, and highlight the role of comprehensive geriatric assessments. We will also review how real-world evidence complements the data gaps from clinical trials of early stage colon cancer.     

Pharmacokinetics of chemotherapy in the older patient.

BACKGROUND: The number of individuals aged 65 years and older is growing rapidly, and the majority of cancers are diagnosed in this age group. Age-related changes in physiology can affect chemotherapy pharmacokinetics and pharmacodynamics in older patients. METHODS: We review the literature regarding the impact of age on the pharmacokinetics of commonly used chemotherapy drugs and discuss age-related changes in physiology and pharmacology that can affect chemotherapy tolerance in older patients. RESULTS: The data on age-related changes in chemotherapy pharmacokinetics are conflicting. While a few studies report age-related differences in chemotherapy pharmacokinetics, most found no significant difference or subtle differences in pharmacokinetics with aging. A difference in pharmacodynamics was commonly seen, however, with older patients at increased risk of myelosuppression and toxicity from age-related decline in organ function. The majority of these studies were performed in a small cohort of patients, thus limiting the generalizability of these results. CONCLUSIONS: Additional studies are needed to address the pharmacokinetics and pharmacodynamics of cancer therapies in the older patient. Multicenter pharmacokinetic studies of adequate sample size, which include a thorough evaluation of physiologic factors and geriatric assessment parameters, would provide further insight into the factors affecting treatment tolerance. These studies would also help to guide appropriate chemotherapy dosing and interventions in order to maximize efficacy and minimize toxicity in the older patient.     

Cancer in the older person

Cancer in the older person is an increasingly common problem, due to the progressive prolongation of the life-expectancy of the Western population. This article reviews the mechanisms associating aging and cancer, age-related changes in cancer biology, assessment of the older person to estimate life-expectancy, treatment tolerance, and medical and social conditions that may interfere with cancer treatment, effectiveness of cancer prevention and cancer treatment in older individuals. A comprehensive geriatric assessment (CGA) is commonly used to predict life-expectancy and functional reserve and to unearth conditions that may jeopardize cancer prevention and treatment. In the interest of cost and time, shortened forms of CGA are being explored. Chemoprevention of cancer is a promising form of prevention that at present has no conclusive clinical indications. Early diagnosis of breast and colon cancer through screening of asymptomatic patients at risk may be beneficial for individuals with a life-expectancy of 5 years or longer. Early detection of lung cancer in ex-smokers is undergoing clinical trials, as this disease is becoming more and more common. Age should not prevent appropriate treatment of cancer in older individuals, especially in those with adequate life-expectancy and functional reserve. The National Cancer Center Network (NCCN) has issued a series of guidelines to minimize the toxicity and promote the effectiveness of cancer in older patients. Important interventions include prevention of neutropaenic infections with filgrastim and peg-filgrastim, prevention of anaemia with epoietin or darbepoietin, and prevention and early management of mucositis.     

The Role of Adjuvant Therapy in the Elderly

Colorectal cancer is the third commonest cancer and second commonest cancer killer in the USA. With a median age at diagnosis of 72 years, it largely affects the elderly population. However, there is a lack of objective data with which to answer clinically relevant questions regarding adjuvant therapy in the geriatric patient population because mainly younger patients are enrolled in clinical trials. Elderly patients are undertreated in the adjuvant setting owing to multiple factors, including physician decision and patient preference. Older patients have different tumor biology, physiologic factors, and social situations to consider in comparison with younger patients. Thus, geriatric patients require more thorough assessment of their functional status and existing medical conditions as they are at risk of increased toxicities from chemotherapy and their ongoing treatment requires vigilance. Elderly patients do benefit from adjuvant chemotherapy, although subgroup analyses show that many do not derive incremental benefit from the addition of oxaliplatin to 5-fluorouracil therapy.     

Management of colorectal cancer in older patients

An increasing body of evidence suggests that geriatric patients can benefit from and tolerate standard chemotherapy similarly to younger patients in the settings of both early- and advanced-stage colorectal cancer. Assessment of this unique population requires more comprehensive evaluation in addition to routine history, physical examination, and laboratory tests. Specific considerations of their physiologic functional changes will help physicians better manage these patients. Ongoing studies are now designed to better understand the decisionmaking process, safety profile, and efficacy of various treatment regimens in geriatric patients.     

Management of the toxicity of chemotherapy and targeted therapies in elderly cancer patients

The elderly form a very heterogeneous group in relation to their general health state, degree of dependence, comorbidities, performance status, physical reserve and geriatric situation, so cancer treatment in the older patient remains a therapeutic challenge. The physiological changes associated with aging increase the risk of developing a serious toxicity induced by chemotherapy treatment, as well as other undesirable consequences as hospitalizations, dependence and non-compliance with treatment, that can negatively affect survival, quality of life and treatment efficacy. The use of hematopoietic growth factors and other active supportive interventions in the elderly can help prevent and/or alleviate these toxicities. However, we have little data on the efficacy and tolerance of support treatments in the older patient. The objective of this work is to review the most frequent toxicities of oncological treatments in the elderly and their management.

     

Nutrition and Aging: a Practicing Oncologist’s Perspective

Malnutrition is common in patients with cancer and is associated with a variety of negative outcomes. These can include reduced treatment tolerance and worsened cancer prognosis. Various aspects of aging, including sensory, physical, or psychosocial changes, place older patients at a particularly high risk for malnutrition, and these geriatric factors must be identified early and addressed. Despite the lack of available evidence on the optimal nutritional interventions for older adults with cancer, the oncologist must be prepared to address the common nutritional concerns that arise in both advanced cancer and survivorship settings. While BMI, weight loss, and serum albumin are commonly used as surrogates of malnutrition, the use of a comprehensive screening tool may promote early identification of disrupted eating patterns and allow for prompt intervention. New digital technologies have also demonstrated promise to improve nutritional assessment capabilities. Use of conventional nutritional support in conjunction with novel nutraceutical and anti-cachexia approaches may enhance the effectiveness of interventions and improve our ability to reverse malnutrition-associated alterations in body composition. Future geriatric-focused nutrition research will be crucial in helping guide our patients and effectively addressing their dietary and lifestyle concerns.     

Prediction of treatment-related toxicity and outcome with geriatric assessment in elderly patients with solid malignancies treated with chemotherapy: a systematic review

IntroductionThe number of older patients with cancer is increasing. Standard clinical evaluation of these patients may not be sufficient to determine individual treatment strategies and therefore Geriatric Assessment (GA) may be of clinical value. In this review, we summarize current literature that is available on GA in elderly patients with solid malignancies who receive chemotherapy. We focus on prediction of treatment toxicity, mortality and the role of GA in the decision-making process.DesignWe conducted a systematic search in PubMed. Studied populations needed to fulfill the following criteria: 65 years or older, diagnosis of solid malignancy, treatment with chemotherapy, submission to GA, either designed to study prediction of treatment toxicity or mortality or to evaluate the role of GA in the decision-making process.ResultsOur search provided 411 publications. Thirteen met the predefined criteria. These studies revealed: (i) up to 64% of elderly patients suffer from severe toxicity caused by polychemotherapy, (ii) Nutritional status, functionality and comorbidity are often associated with worse outcome, (iii) GA reveals (unknown) geriatric problems in more than 50% of elderly patients with cancer and (iv) 21%–53% of chemotherapy regimens are being modified based on GA.ConclusionsIn geriatric oncology, an accurate predictive test to guide anticancer treatment in order to prevent serious toxicity is needed. The value of GA in predicting toxicity and mortality in older patients with cancer undergoing treatment with chemotherapy has not been proven. It may be valuable in revealing geriatric problems but current evidence for its usefulness to guide treatment decisions in this setting is limited. However, we are convinced that GAs should be carried out to optimize treatment strategies in elderly patients with cancer to improve treatment efficacy and minimize toxicity.