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Treatment of Advanced Non–Small-Cell Lung Cancer in Special Populations

Treatment of Advanced Non–Small-Cell Lung Cancer in Special Populations

Only a minority of elderly patients with advanced non- small-cell lung cancer (NSCLC) have been offered palliative chemotherapy, as indicated by clinical surveys beginning in the 1980s. Lilenbaum's thorough review of the treatment of locally advanced and metastatic NSCLC studies in two special populations (elderly and Eastern Cooperative Oncology Group [ECOG] performance status [PS] 2 patients) highlights a new trend seen with the advent of better-tolerated chemotherapy regimens. Key Studies
For patients older than age 70 years with no major comorbidities, the author refers to US cooperative group studies to justify the use of a platinum- based doublet-as would be used in the younger patient population. Alternatively, elderly patients with severe comorbidities and a lower performance status could be treated with single-agent therapy, such as vinorelbine (Navelbine) or gemcitabine (Gemzar), as shown in Gridelli's Elderly Lung Cancer Vinorelbine Italian Study (ELVIS) that assessed for the first time the benefit of a newer chemotherapy agent in older patients.[1] Also of note, given that the majority of elderly lung cancer patients present with unresectable disease, Schild and colleagues discovered that fit elderly patients with locally advanced NSCLC also enjoyed a survival advantage when treated with combinedmodality therapy.[2] Functional vs Chronologic Age
The decision to treat an elderly NSCLC patient with palliative chemotherapy will depend more on the patient's functional age than chronologic age. Lilenbaum recognizes that a favorable functional status portends a good response to chemotherapy. Functional status is one of several components that comprise a comprehensive geriatric assessment.[3] Others include the patient's comorbid medical conditions, cognition, psychological status, social functioning and support, medication history, and nutritional status. The "frail" older patient will likely pose the greatest challenge in choosing a palliative treatment course. Comprising 10% to 25% of people over age 65, frail patients are described as having one or more of the following characteristics: age over 85, serious comorbid medical conditions, dependence in activities of daily living, and at least one of the common geriatric syndromes (delirium, dementia, urinary or fecal incontinence, failure to thrive, a history of an osteoporotic fracture, or social neglect or abuse).[4] To date, there is no standard definition of "frailty" that can be used for anticipating and preventing adverse treatment-related outcomes. For the individual elderly patient, the clinician should have a thorough discussion regarding the benefits and toxicities of the proposed regimen, as well as which, if any, second-line chemotherapy agents would be pursued upon progression of disease. There is no evidence of improved survival or quality of life associated with second- or third-line chemotherapy for advanced NSCLC in this patient population. For patients with impaired performance status, a phase III trial of erlotinib (Tarceva) as second-line therapy for patients with non-small-cell lung cancer revealed an improved median survival among ECOG PS 2 patients receiving erlotinib compared with placebo (4.3 vs 3.3 months).[5] Comparatively, PS 3 patients who received erlotinib fared worse than those who received a placebo (median survival: 1.9 vs 3.1 months). Conclusions
With 60% of all cancers occurring among individuals over age 65, and with the percentage of people over 65 surpassing 20% by 2003, future cooperative trials should place greater emphasis on elderly cancer patients. Non-small-cell lung cancer patients, with their inherent predisposition toward pulmonary and cardiovascular comorbidities, can be particularly vulnerable to the side effects of both doublet and singlet chemotherapy regimens. When caring for the elderly patient with NSCLC, open-ended communication is essential. Compared with their younger counterparts, elderly patients often maintain different attitudes regarding illness, death, and dying.

Disclosures

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

1. The Elderly Lung Cancer Vinorelbine Italian Study Group: Effect of vinorelbine on quality of life and survival of elderly patients with advanced non-small cell lung cancer. J Natl Cancer Inst 91:66-72, 1999.
2. Schild SE, Stella PJ, Geyer SM, et al: The outcome of combined-modality therapy for stage III non-small cell lung cancer in the elderly. J Clin Oncol 21:3201-3206, 2003.
3. Repetto L, Comandini D: Cancer in the elderly: Assessing patients for fitness. Crit Rev Oncol Hematol 35:155-160, 2000.
4. Balducci L, Stanta G: Cancer in the frail patient: A coming epidemic. Hematol Oncol Clin North Am 14:235-250, 2000.
5. Shepherd FA, Pereira J, Ciuleanu TE, et al: A randomized placebo-controlled trial of erlotinib in patients with advanced non-small lung cancer (NSCLC) following failure of 1st line or 2nd line chemotherapy. A National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) trial (abstract 7022). Proceedings and abstracts of the 2004 Annual Meeting of the American Society of Clinical Oncology Available at www.asco.org. Accessed 8/3/04.
 
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