Youth Has No Age: Cancer Treatment for Older Americans

Calendar age and biological age do not always correspond. Pablo Picasso, source of the quote that begins the title of this commentary, lived a notoriously robust and active life through his later decades, dying in his nineties in the midst of a dinner party. In the oncology community, with the advent of targeted therapeutics and better supportive care, the disparity between the two is likely to be increasingly relevant to both research and practice. In this issue of ONCOLOGY, Chiappori et al review data supporting the idea that even in the context of standard cytotoxic chemotherapy, elderly patients with advanced NSCLC experience similar response rates and similar survival benefits to those seen in younger patients. They note that biases excluding elderly patients from clinical trials result in gaps in our knowledge of how to best treat older patients.

A Long-Standing Problem
These authors are certainly not the first to highlight the bias against the inclusion of elderly patients in clinical cancer trials, or the negative impact of this bias on clinical practice. Twenty-eight years ago Carbone and Begg reported generally similar outcomes and toxicity from chemotherapy agents in elderly (≥70) and nonelderly patients, normalized for performance status.[1] Ten years ago, Hutchins et al documented the underrepresentation of elderly patients in cancer treatment trials.[2] These investigators reviewed 164 trials involving 16,000 patients between 1993 and 1996 and found that elderly patients (≥65) accounted for 25% of the patients on trials, a stark underrepresentation of the 63% of US cancer patients in this age demographic.

Both the National Cancer Institute and the National Institute on Aging have recognized the problem and have proposed action to address it.[3,4] Despite tolerating chemotherapy agents as well as younger patients, the elderly are underrepresented in clinical trials, [5-7] and perhaps of greater concern, appear to be undertreated.[8-10] In the modern era, economics are not likely to be a primary explanation for underrepresentation of the elderly in clinical trials. A 2000 presidential executive memorandum mandated Medicare coverage for routine care costs associated with clinical trial participation, a decision which has been credited for a 14% increase in accrual of Medicare participants to federally funded cancer clinical trials.[11] Also perhaps due to this Medicare policy, our own recent data suggests that among patients who consented to participate in therapeutic cancer research, insurance company approval for participation actually is biased in favor of the elderly (P = .0001).[12] While comorbidities exclude some patients from trials, the fit elderly certainly should not be excluded. Trimble and Christian [3] posit at least three factors as contributors to the bias against advanced treatments for elderly cancer patients: (1) lack of an adequate database on how best to treat the fit and frail elderly, (2) inadequate access to optimal cancer care caused by a lack of social support network for the elderly, and (3) a relatively low rate of referral of the elderly to NCI-designated cancer centers. The third of these factors may be of particular relevance to the under-representation of this group in therapeutic research.

The Problem Is Growing
Eliminating these biases is becoming more important as the elderly population grows. Between 2010 and 2030 the US Census Bureau projects that Americas over 70 will grow from one in eleven Americans to one in seven - an 85% increase to a total of 52 million by 2030, from 28 million in 2010.[13]

Promising Paths toward Treating This Growing Population
Three initiatives offer promise in improving care for elderly cancer patients, and are described in more detail below:

(1) Dedicated efforts to increase elderly patient representation in clinical trials in order to develop a database on how best to treat this population, including trials with targeted accrual of patients over 70 years of age.

(2) Inclusion of patients in trials who would otherwise have been excluded based on organ dysfunction and other comorbidities, and studies focused on these traditionally excluded populations.

(3) Innovation in clinical trial management enabling patients at community hospitals to participate in trials of new drugs, combined with active outreach programs that engage physicians in smaller hospitals that are not part of NCI-designated Cancer Centers.

In 2006, in a joint effort to expand the participation of the elderly in cancer research, the National Cancer Institute and the National Institute on Aging established eight centers to do cross-disciplinary studies of cancer and the aging. A current search of the clinicaltrials.gov database (www.clinicaltrials.gov) reveals 83 clinical trials that specifically focus on cancer in the elderly, including several that specifically exclude younger patients. This is a good start, but more could be done among federal funding agencies to actively encourage its grantees to include representative numbers of elderly patients in clinical trials, and to regularly measure and report progress on reducing the bias. While current National Cancer Institute grants involving human subjects mandate reporting of planned and actual participation by gender, race, and ethnicity, and mandate consideration of inclusion of children, the same is not true of the elderly.

Because organ dysfunction is more common in the elderly and because it is often used as an exclusion criterion for clinical trials, specific trials and trial sub-groups are needed to define therapeutic options for this growing population of the “frail elderly” with adequate performance status. In lung cancer research in particular, large-scale systematic studies of standard therapeutic options to define recommended regimens and dose reduction guidelines in the context of varying levels of organ dysfunction should be considered. In the absence of such studies, treating physicians are left to guess at regimens and doses that are likely to be safe, or even to forgo interventional therapy in these patients.

Advances in electronic patient record keeping and communications may enable innovation in clinical trial management, allowing elderly patients to participate in trials without traveling to major academic research centers. One recent National Cancer Institute initiative in this regard is the Community Networks Program, which provides significant financial backing to support centers for reducing disparities through community outreach, research and training.

In addition to facilitating patient access, professional education may play a significant role in these efforts. Elderly patients may be more likely to participate in clinical trials if the physicians advising them are fully aware of the parity in response of the fit elderly and younger patients to chemotherapy. Emerging data on effectiveness of lower doses of standard therapeutics, and on lower toxicity of some of the newer targeted agents, may help referring physicians gain confidence in the safety of and advisability of clinical trial participation for their elderly patients.

Advances in management of cardiac disease and other chronic illnesses, compounded by the aging of the baby boomers, are prompting a seismic shift in cancer demographics in America. As a community, we better get ready for it.

Financial Disclosure:The authors have no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.

References:

References

1. Begg CB, Carbone PP. Clinical trials and drug toxicity in the elderly. The experience of the eastern cooperative oncology group. Cancer 1983;52:1986-1992.

2. 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 1999;341:2061-2067.

3. Trimble EL, Christian MC. Cancer treatment and the older patient. Clin Cancer Res 2006;12:1956-1957.

4. Yancik R, Ries LA, Aging and cancer in america. Demographic and epidemiologic perspectives. Hematol Oncol Clin North Am 2000;14:17-23.

5. Murthy VH, Krumholz HM, Gross CP. Participation in cancer clinical trials: Race, sex-, and age-based disparities. JAMA 2004;291:2720-2726.

6. Talarico L, Chen G, Pazdur R: Enrollment of elderly patients in clinical trials for cancer drug registration: A 7-year experience by the us food and drug administration. J Clin Oncol 2004;22:4626-4631.

7. Townsley CA, Selby R, Siu LL: Systematic review of barriers to the recruitment of older patients with cancer onto clinical trials. J Clin Oncol 2005;23:3112-3124.

8. Du X, Goodwin JS: Patterns of use of chemotherapy for breast cancer in older women: Findings from medicare claims data. J Clin Oncol 2001;19:1455-1461.

9. Schrag D, Cramer LD, Bach PB, et al. Age and adjuvant chemotherapy use after surgery for stage iii colon cancer. J Natl Cancer Inst 2001;93:850-857.

10. Foster JA, Salinas GD, Mansell D, et al. How does older age influence oncologists’ cancer management? Oncologist;15:584-592.

11. Unger JM, Coltman CA, Jr., Crowley JJ, et al. Impact of the year 2000 medicare policy change on older patient enrollment to cancer clinical trials. J Clin Oncol 2006;24:141-144.

12. Klamerus JF, Bruinooge SS, Ye X, et al. The impact of insurance clearance on access to cancer clinical trials at a comprehensive cancer center. Clin Cancer Res 2010;(in press).

13. Vincent G, Velkoff V: The next four decades, the older population in the united states: 2010 to 2050: Current Population Reports, U.S. Census Bureau, 2010, pp 25-1138.