Optimal Pharmacotherapeutic Strategies for Elderly Patients with Advanced Non-Small Cell Lung Cancer

Increases in both life expectancy and cancer incidence with age result in a significant rise in lung cancer rates among elderly patients, with a median age at diagnosis of between 63 and 70 years. However, elderly patients are under-represented in clinical trials and generally receive suboptimal treatment, mainly because of fears about increased toxicity of chemotherapy. Indeed, physiological modification of renal and haematopoietic functions with age together with co-morbidity and associated polypharmacy may alter the metabolism of chemotherapy drugs, resulting in greater toxicity. Moreover, performance status (PS), the main prognostic factor in younger patients, does not correlate well with geriatric indexes such as activities of daily living, cognition and physical performance, and comprehensive geriatric assessment is important in elderly patients. Until 2010, based on the small number of clinical trials designed for elderly patients, monotherapy was the recommended treatment for those with advanced non-small cell lung cancer (NSCLC), whereas for fit younger patients, a platinum-based doublet was and continues to be the recommended first-line therapy. However, at the plenary session of the 2010 Annual Meeting of the American Society of Clinical Oncology, results were presented from a randomized controlled trial conducted by the French Intergroup of Thoracic Oncology that demonstrated that in PS 0-2 patients aged >= 70 years with advanced NSCLC, monthly carboplatin with weekly paclitaxel resulted in significantly longer survival than single-agent therapy (vinorelbine or gemcitabine). It should be noted that even in a priori unfavourable prognostic subgroups (patients with a PS score of 2, those aged >80 years or those with an activities of daily living scale score of <6), doublet therapy was associated with a survival advantage over monotherapy. Thus, the new paradigm of treatment of elderly patients with advanced NSCLC and a PS score of 0-2 should now be monthly carboplatin with weekly paclitaxel. While there have been no trials of second-line therapy for NSCLC specifically in elderly patients, exploratory subgroup analyses indicate that docetaxel, pemetrexed and erlotinib may provide outcomes in elderly patients similar to those reported in younger patients. However, specific second-line therapy trials in elderly patients are required as the elderly patients in trials conducted to date were probably highly selected to fit the inclusion criteria. There is no more room for nihilism in the treatment of elderly patients with advanced NSCLC. Such patients should be evaluated carefully by geriatric indexes and, if they have a PS score of 0-2, may be treated with platinum-based (mostly carboplatin) doublet therapy in the same manner as their younger counterparts. The optimal second line treatment remains to be determined.