|
Advertisement |
|
|
||
 |
|
|||||
|
|||||
|
 |
||||||
|
||||||
|
||||||
|
Originally published as JCO Early Release 10.1200/JCO.2005.10.976 on February 14 2005 © 2005 American Society of Clinical Oncology.
The Frail Are Not Always ElderlyMultidisciplinary Oncology Institute, Genolier, Switzerland 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.1 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.2 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.3 Baka et al,4 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,5 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.6 The European Organisation for Research and Treatment of Cancer has shown that a radiation boost might not be of importance for elderly patients,7 and a recent study suggests that the risk of local relapse is small in some conservatively treated breast cancer patients 70 years or older.8 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.9 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.10 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 al11 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.12 Simplistic approaches, like dose reduction, are not an answer, nor are they needed for many agents.13,14 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.15 While the study of Bajetta et al was not powered to detect the increased toxicity of capecitabine in patients with decreased renal function, it does suggest the importance of this issue, recognized only after the study had started and now included in the summary of product characteristics in the package insert. In this context, one should note that the standard Cockroft-Gault formula, which is used to evaluate a calculated creatinine clearance, is not validated for patients older than 85 years and is not always accurate.16 Baka et al,4 also in this issue of the Journal, show us that the frail are not always the elderly. It has been accepted that the Karnofsky score or the WHO/Eastern Cooperative Oncology Group performance status score identifies patients at high risk, and their study confirms this point. By the end of the second month of observation, only 61.5% of the patients were alive—a significant attrition due to disease progression. Early death is an issue that also affects studies with potentially frail elderly patients, and is a reason to use instruments that can, better than performance status, indicate who is at risk for early complications. Studies with elderly patients are also affected by deaths due to concomitant diseases, a factor discussed already many years ago, and a potential barrier to adjuvant studies.17 The authors also point out how clinicians under-report symptoms, which is another reason to plead for the use of the comprehensive geriatric assessment, which takes into account many important factors that are otherwise poorly assessed. The authors implicitly recognize this, as they discuss the fact that assessment of comorbidity would be helpful in helping to distinguish between a low Karnofsky score related to the lung cancer as opposed to comorbidity. Such a difference, as they state, could have therapeutic implications. The last, but certainly not the least, of the open questions in therapeutic trials of the elderly patient, is obtaining informed consent. Determining decision-making capacity, discussing withdrawing and withholding of interventions, responding to requests for interventions, and allocating health care resources are ethical dilemmas that are often increased because of poor patient-clinician communication.18 Elderly patients may have more difficulty comprehending consent information, and particular attention should be given to compensating for communication and sensory deficits and improving the readability of information sheets and consent forms.10 Author's Disclosures of Potential Conflicts of Interest The author indicated no potential conflicts of interest. REFERENCES 1. Repetto L, Venturino A, Fratino L, et al: Geriatric oncology: A clinical approach to the older patient with cancer. Eur J Cancer 39:870-880, 2003[CrossRef][Medline] 2. Ferrucci L, Guralnik JM, Cavazzini C, et al: The frailty syndrome: A critical issue in geriatric oncology. Crit Rev Oncol Hematol 46:127-137, 2003[Medline]
3. Repetto L, Fratino L, Audisio RA, et al: Comprehensive geriatric assessment adds information to Eastern Cooperative Oncology Group performance status in elderly cancer patients: An Italian Group for Geriatric Oncology Study. J Clin Oncol 20:494-502, 2002
4. Baka S, Ashcroft L, Anderson H, et al: Randomized phase II study of two gemcitabine schedules for patients with impaired performance status (Karnofsky performance status 5. Audisio RA, Bozzetti F, Gennari R, et al: The surgical management of elderly cancer patients: Recommendations of the SIOG surgical task force. Eur J Cancer 40:926-938, 2004[CrossRef][Medline] 6. Pierga JY, Girre V, Laurence V, et al: Characteristics and outcome of 1755 operable breast cancers in women over 70 years of age. Breast 13:369-375, 2004[CrossRef][Medline] 7. Vrieling C, Collette L, Fourquet A, et al: Can patient-, treatment- and pathology-related characteristics explain the high local recurrence rate following breast-conserving therapy in young patients? Eur J Cancer 39:932-944, 2003[CrossRef][Medline]
8. Hughes KS, Schnaper LA, Berry D, et al: Lumpectomy plus tamoxifen with or without irradiation in women 70 years of age or older with early breast cancer. N Engl J Med 351:971-977, 2004 9. Orecchia R, Ciocca M, Lazzari R, et al: Intraoperative radiation therapy with electrons (ELIOT) in early-stage breast cancer. Breast 12:483-490, 2003[CrossRef][Medline] 10. Bayer A, Fish M: The doctor's duty to the elderly patient in clinical trials. Drugs Aging 20:1087-1097, 2003[CrossRef][Medline]
11. Bajetta E, Procopio G, Celio L, et al: Safety and efficacy of two different doses of capecitabine in the treatment of advanced breast cancer in older women. J Clin Oncol 23:2155-2161, 2005 12. Wildiers H, Highley MS, de Bruijn EA, et al: Pharmacology of anticancer drugs in the elderly population. Clin Pharmacokinet 42:1213-1242, 2003[CrossRef][Medline]
13. Kohne CH, Grothey A, Bokemeyer C, et al: Chemotherapy in elderly patients with colorectal cancer. Ann Oncol 12:435-442, 2001 14. Chau I, Norman AR, Cunningham D, et al: Elderly patients with fluoropyrimidine and thymidylate synthase inhibitor-resistant advanced colorectal cancer derive similar benefit without excessive toxicity when treated with irinotecan monotherapy. Br J Cancer 91:1453-1458, 2004[CrossRef][Medline] 15. Repetto L, Biganzoli L, Koehne CH, et al: EORTC Cancer in the Elderly Task Force guidelines for the use of colony-stimulating factors in elderly patients with cancer. Eur J Cancer 39:2264-2272, 2003[CrossRef][Medline]
16. Marx GM, Blake GM, Galani E, et al: Evaluation of the Cockroft-Gault, Jelliffe and Wright formulae in estimating renal function in elderly cancer patients. Ann Oncol 15:291-295, 2004 17. Castiglione M, Gelber RD, Goldhirsch A: Adjuvant systemic therapy for breast cancer in the elderly: Competing causes of mortality. International Breast Cancer Study Group. J Clin Oncol 8:519-526, 1990[Abstract]
18. Mueller PS, Hook CC, Fleming KC: Ethical issues in geriatrics: A guide for clinicians. Mayo Clin Proc 79:554-562, 2004
Related Articles
This article has been cited by other articles:
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||||||||||
|
|||||||||||
|
|
Copyright © 2005 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
|
70) and advanced non–small-cell lung cancer. J Clin Oncol 23:2136-2144, 2005
