Non-small-cell lung cancer (NSCLC) is primarily a disease of older adults, but because this group is underrepresented in clinical trials, the best treatment for older patients with advanced disease is uncertain. One factor contributing to under-treatment of older patients may be an assumption that they're more vulnerable to the toxic side effects of medication. However, until now, the rate of clinically important adverse events associated with patient age was not known.
In a study in the Journal of Clinical Oncology (2010;28:620–627), a team led by Elizabeth A. Chrischilles, PhD, found that older patients who received chemotherapy had fewer adverse events before treatment than younger adults did, suggesting that the older adults who received chemotherapy were more fit at the time of diagnosis than their younger counterparts. However, the rates of adverse events during chemotherapy in those 65 and older were significantly higher, independent of comorbidity.
Older patients were also less likely to receive more toxic platinum-based regimens. The results highlight the need for physicians to make explicit the potential trade-offs between symptom management and treatment toxicity when counseling patients on treatment options, the authors concluded.
The research subjects were 1,371 patients with newly diagnosed Stages IIIB and IV NSCLC who did not receive primary surgery, selected from the population-based cohort studied by the CanCORS (Cancer Care Research Outcomes and Surveillance) Consortium. Patients were interviewed at enrollment and at 12 months after diagnosis (because of the severity of illness and high mortality rate, surrogate versions of the baseline interviews were also developed); additional data were abstracted from patient medical records and from surveys of treating physicians and informal caregivers.
The researchers analyzed the association between age group (younger than 55, 55 to 64, 65 to 74, and 75 or older) and receipt of chemotherapy and made adjustments for clinical and demographic variables.
The subgroup of patients (58%) who received at least one course of chemotherapy was further analyzed to determine their rate of adverse medical events (defined as first event occurrences) before, during, and after treatment.
Almost half of the patients received radiation therapy, and, of these, 58% also received chemotherapy. Data were collected between 2003 and 2005; targeted molecular therapy, not then widely available, was used by less than 3% of patients.
Age was found to be strongly and inversely related to whether or not patients received chemotherapy; after adjustment, 72% of patients younger than 55 received chemotherapy, but only 47% of those in the oldest age group did.
Other findings included the following: while 84% of patients younger than 55 received a platinum-based treatment, only 71% of those 75 and older did. During the period from diagnosis to the start of chemotherapy, older adults were less likely than younger adults to have had a clinically important adverse event; only 9.2% of those age 75 and older had one, whereas 18.6% of those younger than age 55 did.
However, despite their overall better fitness, significantly more of the older adults who chose to receive chemotherapy experienced adverse events during treatment. The highest rate of adverse events (42.4%) was among those 65 to 74; the lowest (30.6%) was among those younger than 55.
Overall, approximately one-third of patients had at least one kind of adverse event (there were 365 events among 249 patients during 100,769 person-days of chemotherapy). There were no age interactions with comorbidities in any age group.
Patient Education Key to Understanding Options
While these findings largely confirmed the researchers' expectations, there are important implications for patient education and future research, the team said.
As Dr. Chrischilles, Professor of Epidemiology and Associate Director for Population Science at the Holden Comprehensive Cancer Center at the University of Iowa College of Public Health, said in an interview, “I think it's quite clear that older people are less likely to be treated with chemotherapy. The reason for chemotherapy in this setting is to reduce the burden of disease. If you're not getting chemotherapy, you're not getting that benefit.”
Older, more vulnerable patients often don't fully understand how to compare the increased risk of treatment toxicity and the increased disease symptoms that result from not getting the treatment. “It's a personal decision, and we want to make sure that we fully discuss how effective the chemotherapy is and what toxicities might be expected when they're making this decision, so they know they're making this tradeoff,” she said.
The study did not analyze decreased tumor burden and increased quality of life resulting from treatment, but existing research suggests that cancer patients may regard reduced disease burden as more important than avoidance of toxicity, Dr. Chrischilles continued.
“It's not conclusive, but it does suggest that before we decide not to treat people because of toxicity, we ought to talk to them about their preferences.”
In an accompanying editorial, “Treatment of Older Patients With Non-Small-Cell Lung Cancer: Walking the Therapeutic Tightrope,” George R. Simon, MD, Director of Thoracic Oncology at Fox Chase Cancer Center, noted that slightly more than half of the nearly 110,000 adults diagnosed with lung cancer last year were older than 70.
“The population of the United States is aging, and we are going to see more and more elderly patients with lung cancer,” he said in a telephone interview. “I think that we need to design clinical trials that are specifically tailored for the elderly.”
Patient education is key, he added. “Treatment selection should come out of a two-sided discussion and arrive at a mutually acceptable treatment strategy. First, the physician needs to assess how healthy the older person is. And then the physician has to present the treatment options, with the clear understanding that the less aggressive regimen may result in less toxicity but also come with a possible decrease in efficacy.”
In his editorial, Dr. Simon wrote: “Counseling patients about the anticipated adverse effects and their early identification and palliation could further mitigate the impact of these toxicities on quality of life and potentially even on survival.”
Implications for Future Research
To help physicians achieve an optimum balance between increased life expectancy and better quality of life, Dr. Chrischilles stressed the need for additional research in this population. “Quality of life is a very broad concept that's influenced by symptom burden and also including physical, social, cognitive, and emotional function. Perhaps what we need is a better assessment of the quality-of-life impact of these treatments in real-world practice among older and more complicated patients.
And beyond that is the interpretation of quality-of-life data for clinical decision-making,” she said.
Better Understanding of Pharmacokinetics of New Drugs in Older Patients
Dr. Simon said another priority for future research is to develop a better understanding of the pharmacokinetics of new drugs in older patients. “As one ages, organ functions decline, and the ability to eliminate drugs also declines, so the drugs stay in the body longer and cause more side effects.”
His editorial noted recent findings in targeted molecular therapy research and said that the higher incidence of adverse events in older patients would likely hold true for the newer therapies as well. “These findings, however, should not preclude the treatment of older patients with optimal regimens—rather, the focus should be on finding ways to optimally dose older patients and to abrogate toxicity by taking advantage of the available supportive measures.”
‘Oncologists Tend to Minimize the Side Effects’
Asked for her opinion for this article, Joan H. Schiller, MD, Chief of Hematology and Oncology and Deputy Director of the Simmons Comprehensive Cancer Center at the University of Texas Southwestern Medical Center, said that oncologists sometimes minimize the side effects of chemotherapy: “Clinicians tend to forget that patients going onto a clinical study are often ‘the best of the best,’ so to speak. The patients tend to be healthier and less representative of the total population, so we have to be careful in extrapolating the results of those tests.
“The study really does point out the need for discussing the goals of treatment with each individual patient. If quality of life is the major goal, that should really be taken into consideration when discussing treatment options.”
Dr. Chrischilles is enthusiastic about continuing in this line of research: “I think this whole area of age and treatment intensity and treatment outcomes is really fascinating. It's important not only in oncology but in many situations involving elderly patients or others with complex comorbidities,” she said.
“Those who might benefit the most from treatment are often the least likely to receive it. So this is a pervasive issue and I think the relatively new area of comparative effectiveness research may help us to expand upon the evidence base in real-world situations.”