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Originally published as JCO Early Release 10.1200/JCO.2005.05.4502 on March 27 2006 © 2006 American Society of Clinical Oncology.
Cancer in the Elderly Population: The Protection RacketDepartment of Solid Tumor Oncology and Geriatric Oncology Clinic, Cleveland Clinic Taussig Cancer Center, Cleveland, OH;
Section of Geriatric Medicine, Cleveland Clinic and Geriatric Oncology Clinic, Cleveland Clinic Taussig Cancer Center, Cleveland, OH For the past century, patients of older age have constituted one of the substantially underserved populations in cancer care,1 a puzzling dichotomy when one considers that cancer is classically a disease of the older population and that the proportion of these patients in the community is increasing.2 The reasons for this imbalance are protean—older patients are traditionally conservative, have a somewhat nihilistic view of cancer treatment, and often have fewer resources needed to gain optimal care. The situation has been compounded by the medical protectionism that has been fostered by the government—in the past, studies of the National Cancer Institute (Bethesda, MD) have excluded patients over the age of 65 or 70 years, few provisions have been made for the additional requirements for participation in clinical trials by older patients, and government agencies have interfered with the implementation of studies focused on them by limiting the aggression of proposed treatment protocols in favor of more conservative, gentler regimens. In addition, physicians have been notoriously reluctant to refer older patients for clinical trials, and as a result of governmental disincentives, have avoided designing trials specifically for older patients. It is clear that the use of optimal treatment for curable cancers in elders is ultimately much less morbid than the implementation of attenuated strategies that sacrifice the chance of cure in exchange for reduced acute toxicity. Although this is particularly important in the management of localized disease, our studies from more than 15 years ago showed quite clearly that chemotherapy can be very useful in curing or palliating elderly populations with advanced cancer.3,4 The choice of treatment must be predicated on consideration of the untreated natural history of the disease, the efficacy and toxicity of the proposed treatment, and the active life expectancy and comorbidities of the patient—essentially a cost-benefit analysis. In the setting of advanced disease, the efficacy and toxicity of treatment are influenced by several factors, including age, comorbidity and organ function, other medications, and adherence to medication schedules. Unfortunately, this information is not available for many of the drugs available for cancer treatment in very elderly populations, largely because the acquisition of these data requires time and commitment on the part of investigators and patients. The investigators of Cancer and Leukemia Group B are to be complimented for their creativity in modifying pharmacologic sampling schedules, and thus in completing this important study that shows the variability of pharmacokinetics of paclitaxel in older patients, with the general reduction of clearance of this agent with increasing age.5 However, there was no attempt at direct comparison with cohorts of patients younger than 50 years, to allow these data to be set into full context. As the investigators acknowledge, it is difficult to discern the cause for the pharmacologic changes—comorbid conditions, other medications, or sample size errors. Some of this information will become available when the investigators of the Southwest Oncology Group (SWOG) have reported their studies of efficacy, toxicity, the impact of comorbidity, pharmacokinetics and pharmacodynamics of paclitaxel, gemcitabine, and other cytotoxics in patients with advanced cancer (SWOG trials S0028, S0029, and S0030). These studies have taken a long time to complete accrual, perhaps because of the pharmacologic measurement schedules, in contrast to SWOG S0031, a study of chemotherapy in elderly patients without pharmacologic sampling. What is clear is that we must be better prepared for the imminent wave of elderly patients, the result of the fecundity of the postwar era. Increasing numbers of elderly patients, including many with smoking-related disorders, will produce unprecedented numbers of patients requiring active cancer care and we are not ready for them. What we need is data—on the role of innovations in surgery and radiotherapy for older patients, optimal doses and schedules of cytotoxics, cost-benefit analyses of treatment of elders, the potential role of alternative and complementary strategies, and the utility of some of the newer targeted therapies. Unless we take this challenge seriously, and actively prosecute clinical trials in the elderly, we will not be ready, and we will continue to provide suboptimal care. To achieve these goals, we must change our paradigms: government and health insurance industry payers must more actively support clinical trials targeted to older populations; physicians must actively recruit elderly patients to these trials and desist from factitious and ill-considered medical protectionism; and patient advocacy groups and the Gray Power movement must focus on this important health care issue. Without appropriate research and well-constructed clinical trials focused on elderly cancer patients, both healthy and infirm, we cannot provide this growing population with optimal and humane care. The continued acceptance of lower standards of care for elderly patients, predicated on a refusal to acquire accurate information on their needs, will be judged very poorly in medical history. Authors' Disclosures of Potential Conflicts of Interest The authors indicated no potential conflicts of interest. Author Contributions
REFERENCES
1. Hutchins LF, Unger JM, Crowley JJ, et al: Underrepresentation of patients 65 years of age or older in cancer treatment trials. N Engl J Med 341:2061-2067, 1999 2. Raghavan D, Weiner J, Lipson L: Cancer in the Elderly, in Souhami RL, Tannock IF, Horiot P (eds): Oxford Textbook of Oncology (2nd Ed). London, Oxford, Oxford University Press, 2002, pp 863-874 3. Raghavan D, Grundy R, Greenaway TM, et al: Pre-emptive (neo-adjuvant) chemotherapy prior to radical radiotherapy for fit septuagenarians with bladder cancer: Age itself is not a contra-indication. Br J Urol 62:154-159, 1988[Medline] 4. Findlay M, Griffin A-M, Raghavan D, et al: Retrospective review of chemotherapy for small cell lung cancer in the elderly: Does the end justify the means? Eur J Cancer, 27:1597-1601, 1991[Medline] 5. Lichtman SM, Hollis DR, Miller AA, et al: Prospective evaluation of the relationship of patient age and paclitaxel clinical pharmacology: Cancer and Leukemia Group B (CALGN 9762). J Clin Oncol 24:1846-1851, 2006
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Copyright © 2006 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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