|
Advertisement |
|
|
||
 |
|
|||||
|
|||||
|
 |
||||||
|
||||||
|
||||||
|
Journal of Clinical Oncology, Vol 26, No 8 (March 10), 2008: pp. 1387-1388 © 2008 American Society of Clinical Oncology. DOI: 10.1200/JCO.2007.15.7677
Long Overdue: Phase II Studies in Older Cancer Patients: Where Does the FDA Stand?H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
Geriatric Oncology Consortium, Baltimore, MD To the Editor: The phase II study of uracil-tegafur in elderly patients by Hochster et al1 and the thoughtful editorial of Hurria2 deserve commendation for highlighting one of the major deficiencies in medical oncology today: the scarcity of information related to the pharmacology and the toxicity of antineoplastic agents in older individuals. As Hurria emphasizes in her commentary, and as Hochster et al demonstrated in their trial, phase II studies are the proper venue for collecting this information. Although older patients should not be excluded from phase I trials, phase I trials limited to older patients may unnecessarily delay the development of life-saving drugs. In our opinion, phase II trials represent the best opportunity to both establish whether antineoplastic agents have the same efficacy and toxicity in older and younger patients, and identify age-related pharmacokinetic changes. It is abundantly clear that the risk and severity of some forms of toxicity, such as myelodepression, mucositis, neurotoxicity, and cardiotoxicity increase with age.3 In the meantime, as the absorption of nutrients declines with age, it is reasonable to hypothesize that the bioavailability of oral drugs is reduced in the elderly. Likewise, phase II studies may be the best opportunity to assess the influence of liver function which declines with age on the area under the curve of drugs undergoing hepatic metabolism.3 Hurria emphasizes that approximately 60% of all cancers occur in patients age 65 and older, whereas the average age of patients involved in clinical trials is at least 10 years younger than that. Thus, in reality, an older patient treated with a United States Food and Drug Administration (FDA)-approved agent could be considered a trial given that information obtained from younger patients may not be applicable to older patients. We would strongly encourage the FDA to consider mandating phase II trials of new agents for older people, in view of the abundant evidence that age is associated with significant pharmacologic changes, and that data obtained in young adults should not be applied automatically to the older ones. A government intervention appears necessary. We would also like to challenge the pharmaceutical industry to start on its own studies of older individuals. Given the high proportion of older cancer patients receiving therapy, it is equally important to demonstrate the effectiveness and safety of antineoplastic drugs in younger and older populations. We sincerely hope that the study of Hochster et al will inspire the FDA to take action long overdue. This has become even more urgent with the current evidence that age may be a risk factor for late complications of cancer treatment such as acute myeloid leukemia4 and chronic cardiomyopathy.5 In conclusion, we would like to emphasize Hurria’s suggestion that future studies in older individuals include the estimate of a patient’s physiologic age, based on functional and biochemical parameters that have been widely described in the last few years.6 We, the members of the Geriatric Oncology Consortium, are committed to conducting clinical trials in older individuals by assessing their physiologic age and their particular age-related needs. AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The author(s) indicated no potential conflicts of interest. REFERENCES
1. Hochster HS, Luo W, Popa EC, et al: Phase II study of uracil-tegafurwith leucovorin in elderly ( 2. Hurria A: Incorporation of geriatric principles in oncology clinical trials. J Clin Oncol 28:5350-5351, 2007 3. Balducci L: Cancer chemotherapy in the older person, in Balducci L, Ershler WB, DeGaetano G (eds): Blood Disorders in the Elderly. Cambridge, MA, Cambridge University Press, 2008, pp 225-255 4. Patt DA, Zigang D, Shenying F, et al: Acute myeloid leukemia after adjuvant breast cancer therapy: Understanding the risk. J Clin Oncol 25:3871-3876, 2007 5. Pinder MC; Zhigang D; Goodwin JS, et al: Congestive heart failure in older women treated with adjuvant anthracycline therapy for breast cancer. J Clin Oncol 25:3308-3315, 2007 6. Balducci L, Beghe C: From fitness to frailty: Toward a nosologic classification of the older aged person, in Balducci L, Ershler WB, DeGaetano G (eds): Blood Disorders in the Elderly. Cambridge, MA, Cambridge University Press, 2008, pp 39-57
Related Articles
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||||||||||
|
|||||||||||
|
|
Copyright © 2008 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
|
75 year old) patients with colorectal cancer: ECOG1299. J Clin Oncol 25:5397-5402, 2007
