Commentary (Hurria/Kris): Treatment of Non–Small-Cell Lung Cancer in Older Persons

January 1, 2003

Drs. Basche and Kelly presentan excellent comprehensivereview of the treatment ofnon–small-cell lung cancer in olderpersons. Articles such as this, whichfocus on the older patient, are of paramountimportance for several reasons.First, cancer is a disease ofaging, with an 11-fold increased incidenceand a 16-fold increase in cancer-related mortality among patientsover age 65 compared to those under65.[1] Second, the population is aging,and in the year 2030, approximately22% will be over 65.[1] Third,data on older cancer patients are limitedsecondary to an underrepresentationof this population in clinicaltrials.[2,3] Based on these facts, acomprehensive review of the availabledata is important, especially toguide future research.

Drs. Basche and Kelly present an excellent comprehensive review of the treatment of non-small-cell lung cancer in older persons. Articles such as this, which focus on the older patient, are of paramount importance for several reasons. First, cancer is a disease of aging, with an 11-fold increased incidence and a 16-fold increase in cancer- related mortality among patients over age 65 compared to those under 65.[1] Second, the population is aging, and in the year 2030, approximately 22% will be over 65.[1] Third, data on older cancer patients are limited secondary to an underrepresentation of this population in clinical trials.[2,3] Based on these facts, a comprehensive review of the available data is important, especially to guide future research.

Single-Agent vs Combination Chemotherapy in Lung Cancer

Studies to date demonstrate a benefit to treating older patients with non-small-cell lung cancer (NSCLC) with chemotherapy. However, the question of whether to use singleagent or multiagent chemotherapy has not been definitively answered.

As described by Drs. Basche and Kelly, the Elderly Lung Cancer Vinorelbine Italian Study (ELVIS) demonstrated that older NSCLC patients treated with vinorelbine (Navelbine) showed improvement in survival, lung cancer symptoms, and pain, compared to patients who received best supportive care.[4] The Multicenter Italian Lung Cancer in the Elderly Study (MILES) found no difference in survival or quality of life among older patients with NSCLC who received combination chemotherapy with gemcitabine (Gemzar)/vinorelbine vs those who received vinorelbine alone or gemcitabine alone.[5]

More recently, a study presented at the 2002 meeting of the American Society of Clinical Oncology by Dr. Lilenbaum and colleagues on behalf of the Cancer and Leukemia Group B (CALGB) demonstrated a survival benefit for the combination of carboplatin (Paraplatin) and paclitaxel compared to paclitaxel alone in patients with stage IIIB or IV NSCLC.[6] A subset analysis of patients over 70 also demonstrated a benefit for combination chemotherapy, although this did not reach statistical significance secondary to lack of power, given the smaller number of patients in this subset.

Possible explanations for the discrepant results between the MILES and CALGB studies include the following: (1) The two studies used a different combination of chemotherapy drugs (a platinum combination was not used in the MILES trial); (2) Data on the older patients in the CALGB study were based on a subset analysis of older patients, and therefore, further studies are needed to validate these results. The benefit of single-agent vs combination chemotherapy with a platinum doublet in older patients with lung cancer should be explored further.

In any article that discusses the older patient population, the question of what constitutes "older" is raised. Often, an arbitrary cutoff of age greater than 65 or 70 is chosen; however, chronologic age is an inadequate descriptor of an older patient. Two patients of the same chronologic age can clearly have different functional ages. Although the concept of functional age is much more difficult to describe, it can provide important prognostic information that is not suggested by chronologic age alone.

Geriatric Assessment

A geriatric assessment can help determine a patient's functional age. It includes an evaluation of functional status (ability to be independent in daily tasks at home and in the community), other comorbid medical conditions, nutritional status, cognition, psychological function, and social support. Each of these components of a geriatric assessment can serve as indicators of mortality or morbidity, independent of treatment.[7-13] As we design future clinical trials, geriatric assessment should be incorporated into the initial assessment of all older patients.

Geriatric assessment can also be used as a means of following a patient's progress during treatment. One of the greatest fears expressed by older patients is that of losing functional independence as a consequence of their disease or treatment. This fear is justified in that functional dependence in itself is an independent predictor of mortality.[8] Performing a geriatric assessment at regular intervals during the course of an older patient's treatment will provide a more detailed picture of the impact of treatment or disease on that patient's daily life. This approach argues for a closer collaboration between geriatricians and oncologists in the care of older patients.

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.

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Hutchins LF, Unger JM, Crowley JJ, et al:Underrepresentation of patients 65 years of ageor older in cancer-treatment trials. N Engl JMed 341:2061-2067, 1999.

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The Elderly Lung Cancer Vinorelbine ItalianStudy Group: Effects of vinorelbine on qualityof life and survival of elderly patients withadvanced non-small-cell lung cancer. J NatlCancer Inst 91:66-72, 1999.

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Gridelli C, Perrone F, Cigolari S, et al:The MILES (Multicenter Italian Lung Cancerin the Elderly Study) phase 3 trial: Gemcitabine+ vinorelbine vs vinorelbine and vs gemcitabinein elderly advanced NSCLC patients(abstract 1230). Proc Am Soc Clin Oncol20:308a, 2001.

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Lilenbaum RC, Herndon J, List M, et al:Single-agent (SA) versus combination chemotherapy(CC) in advanced non-small cell lungcancer (NSCLC): A CALGB randomized trialof efficacy, quality of life (QOL), and costeffectiveness(abstract 2002). Proc Am Soc ClinOncol 21:48b, 2002.

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