The Frail Are Not Always Elderly
Authors: Matti S. Aapro
Journal: Journal of Clinical Oncology (2005)

The oncology community has failed, until recently, to develop adequate studies addressing important issues in adult patients with special needs. Before addressing in more detail the two excellent articles appearing in this issue of the Journal of Clinical Oncology, let us consider the general issue of the elderly patient, and of patients who have very similar problems such as those whose organ function is not within “normal limits.” One should first ask the question: who is an elderly patient? While some regulatory authorities define elderly as a person older than 65 years, clinicians clearly understand that the definition of elderly is related to the (patho)physiology of aging. The aging patients will present variable declines in organ function, and some, at age 75 years, will be as fit if not even more fit than many at age 60 years. This is the reason why geriatricians have taught us to objectively evaluate an elderly person, independent of age. Such comprehensive geriatric evaluations might not be necessary for all patients, and their use in oncology is still under evaluation. They do, however, bring more information than is available in most standard clinical assessments. Baka et al, in this issue of the Journal, used a comprehensive geriatric assessment, which, with its multidimensional objective evaluation, is superior to performance status, a recognized factor indicating risk of toxicity and loss of activity of cytotoxic agents. Surgeons and anesthesiologists have also recognized the importance of adequately addressing the questions posed by the treatment of elderly cancer patients, and radiation therapists have shown that, for some cancers, the changes in tumor biology will lead to different therapeutic decisions as patients age, as exemplified by studies in breast cancer. The European Organisation for Research and Treatment of Cancer has shown that a radiation boost might not be of importance for elderly patients, and a recent study suggests that the risk of local relapse is small in some conservatively treated breast cancer patients 70 years or older. In that study, patients had clinical stage I (T1N0M0 according to the TNM classification), estrogen receptor–positive breast carcinoma treated by lumpectomy, with random assignment to tamoxifen plus radiation therapy (317 women) or tamoxifen alone (319 women). The only significant difference between the two groups was in the rate of local or regional recurrence at 5 years (1% in the group given tamoxifen plus irradiation and 4% in the group given tamoxifen alone; P .001). There were no significant differences between the two groups with regard to the rates of mastectomy for local recurrence, distant metastases, or 5-year overall survival rates (87% in the group given tamoxifen plus irradiation and 86% in the tamoxifen group; P .94). The authors concluded that avoiding radiation was a reasonable choice for these patients. This was thus a study responding to an important question in the care of the elderly: is the burden of standard external-beam radiation necessary? Another answer may lie in intraoperative radiation—a promising approach. Barriers to participation of elderly or otherwise physiologically impaired patients in clinical cancer trials have included complex protocols with onerous outcome measures, a research that until recently focused on therapies involving substantial toxicity; restrictive entry criteria unnecessarily excluding concurrent conditions and medication; and patients’ and families’ limited expectations of benefits and lack of financial, logistic, and social support. Many drugs that have become recently available have adverse effect profiles that make them attractive for evaluation in physiologically impaired populations. In this issue of the Journal, Bajetta et al evaluate an oral fluoropyrimidine, capecitabine. Their study exemplifies an issue encountered in many studies addressing “special” populations: a careful assessment of the potential for pharmacologic/pharmacodynamic changes is needed, as early as possible. Simplistic approaches, like dose reduction, are not an answer, nor are they needed for many agents. Dose reductions should also be avoided during curative treatments, and adequate use of growth factors in the elderly can overcome some of the toxicities that would lead to a dose reduction. While the study of Bajetta et al was not powered to detect the increased toxicity of capecitabine in patients with decreased JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 23 NUMBER 10 APRIL 1 2005