Corey J. Langer, MD, FACP

Lung cancer is the leading cause of cancer-related mortality. Improved understanding in the molecular biology and genetics of lung cancer has resulted in the identification of individual genes, gene expression profiles, and molecular pathways that may be useful for clinical management decisions.

A significant proportion of patients with non-small cell lung cancer (NSCLC) present with locally advanced, unresectable disease. For the most part, fit patients with this diagnosis are treated with combined-modality therapy. Relatively few are rendered resectable. Over the past two decades, combination chemotherapy and radiation, preferably concurrent chemoradiation, has emerged as the standard of care. However, survival gains have been offset, to some extent, by local, normal-tissue, in-field toxicity, particularly esophagitis and pneumonitis.

Elderly patients with stage I-III non-small-cell lung cancer (NSCLC) constitute a peculiar patient population and need specific therapeutic approaches. Limited resections are an attractive alternative for elderly patients with resectable NSCLC because of the potential reduction in postoperative complications. Curative radiation therapy is an acceptable alternative for elderly patients who are unfit for or refuse surgery. Hypofractionated stereotactic body radiation therapy is of particular interest for this population because of its favorable tolerance.

With the aging of the Western population, cancer in the older person is becoming increasingly common. After considering the relatively brief history of geriatric oncology, this article explores the causes and clinical implications of the association between cancer and aging. Age is a risk factor for cancer due to the duration of carcinogenesis, the vulnerability of aging tissues to environmental carcinogens, and other bodily changes that favor the development and the growth of cancer. Age may also influence cancer biology: Some tumors become more aggressive (ovarian cancer) and others, more indolent (breast cancer) with aging. Aging implies a reduced life expectancy and limited tolerance to stress. A comprehensive geriatric assessment (CGA) indicates which patients are more likely to benefit from cytotoxic treatment. Some physiologic changes (including reduced glomerular filtration rate, increased susceptibility to myelotoxicity, mucositis, and cardiac and neurotoxicity) are common in persons aged 65 years and older. The administration of chemotherapy to older cancer patients involves adjustment of the dose to renal function, prophylactic use of myelopoietic growth factors, maintenance of hemoglobin levels around 12 g/dL, and proper drug selection. Age is not a contraindication to cancer treatment: With appropriate caution, older individuals may benefit from cytotoxic chemotherapy to the same extent as the youngest patients.

Lilenbaum’s paper highlightingrecent controversies in the managementof advanced non–small-cell lung cancer (NSCLC) inthe elderly and in vulnerable performancestatus (PS) populations is bothtimely and relevant. A recent Surveillance,Epidemiology and End Results(SEER) analysis suggests that nearly50% of all patients diagnosed withNSCLC are 70 years of age or older.Non–small-cell lung cancer generallypeaks in incidence in the elderly, andthe population of the United States iscontinually aging, with nearly 20%expected to be over age 65 by theyear 2030.[1]

New agents with improved systemic activity are needed for the treatmentof lung cancer. Irinotecan (Camptosar) is a promising agent inadvanced non–small-cell (NSCLC) and small-cell lung cancer (SCLC).In a Japanese phase III trial of advanced NSCLC, irinotecan oririnotecan/cisplatin demonstrated a significant survival advantage comparedto the standard of vindesine/cisplatin. Similar North Americanphase III trials focusing on irinotecan’s role in NSCLC are under way.Ongoing trials have also been launched to corroborate the significantsurvival advantage reported by a Japanese phase III trial for irinotecan/cisplatin vs standard etoposide/cisplatin in extensive SCLC. Currentand planned trials in NSCLC with irinotecan in combination withgemcitabine (Gemzar), the taxanes, and other new agents, and thoracicradiotherapy should also provide useful clinical data. Moreover,trials in SCLC are investigating the rationale of combining irinotecanwith a platinum agent as a component of chemoradiotherapy regimens.Promising data from these and other studies will further elucidate arole for irinotecan in the management of lung cancer.

Dr. Alan Sandler’s sweeping review of the role of irinotecan (CPT-11, Camptosar) in the treatment of small-cell lung cancer (SCLC) leaves few stones unturned. Some perspective, however, is necessary. To date, with the exception of the Japan Clinical Oncology Group trial, which demonstrated the superiority of irinotecan in combination with cisplatin compared to standard therapy with etoposide and cisplatin, no other new platinum agent combination has proven superior to standard therapy in the treatment of extensive SCLC.[1] The Noda study, published recently in the New England Journal of Medicine, has sparked considerable interest and anticipation in the medical oncology community.

Irinotecan (CPT-11, Camptosar), either alone or in combination with cisplatin (Platinol), has demonstrated activity in advanced non-small-cell lung cancer (NSCLC). In single-agent studies, response rates as high as 35%

Topoisomerase I inhibitors have demonstrated significant activity in non-small-cell lung cancer. In phase II studies, particularly in Japan, single-agent irinotecan (Camptosar, CPT-11) has produced response rates as high