An Article published Online First by The Lancet concludes that, despite increased toxic effects, platinum-based doublet chemotherapy is associated with survival benefits compared with monotherapy in elderly patients with non-small-cell lung cancer (NSCLC), and thus the current treatment strategy for these patients (monotherapy only) should be reconsidered. The Article is by Professor Elisabeth Quoix, Department of Chest Diseases, Hopitaux Universitaires de Strasbourg and Université de Strasbourg, France, and colleagues.
Lung cancer is the leading cause of cancer-related death in men worldwide, and in women in the USA it has been the leading cause since 1987. A substantial increase in life expectancy in the general population, with its concomitant increase in the risk of cancer, has led to a notable rise in the incidence of lung cancer in elderly people. As a result, the median age at diagnosis of lung cancer in developed countries is currently 63 to 70 years.
Many elderly people might not receive the most appropriate treatment in practice, possibly because of the pessimism of the doctors and the patients and their relatives about the relevance of treatment or drug-related toxic effects. Platinum-based doublet chemotherapy is recommended to treat advanced NSCLC in fit, non-elderly adults, but monotherapy is recommended for patients older than 70 years. In this study, the authors compared carboplatin and paclitaxel doublet chemotherapy regimen with monotherapy in elderly patients with advanced NSCLC.
The randomised phase 3 trial enrolled 451 patients, with 226 receiving monotherapy and 225 doublet chemotherapy. Median age was 77 years and median follow-up was 30 months. Median overall survival was 10•3 months for doublet chemotherapy and 6•2 months for monotherapy; 1-year survival was 45% and 25%, respectively. Toxic effects were more frequent in the doublet chemotherapy group than in the monotherapy group. The most frequent of these adverse effects were depleted white blood cell count (48% of doublet therapy group versus 12% monotherapy) and feelings of weakness (10% in doublet group versus 6% monotherapy).
The authors point out that previous randomised trials done specifically in elderly patients with advanced NSCLC provide evidence that these patients should be treated with monotherapy, as was borne out by the 2004 American Society of Clinical Oncology guidelines that were in place at the beginning of this new work. But the authors conclude: "Most post-hoc subgroup analyses of elderly patients enrolled in clinical trials with no upper limit of age, however, suggested that fit elderly patients might gain similar benefits to their younger counterparts from platinum-based doublet chemotherapy. Our study of carboplatin and paclitaxel doublet chemotherapy versus gemcitabine or vinorelbine monotherapy showed a survival benefit with the doublet chemotherapy. We believe that treatment current paradigm for elderly patients with advanced non-small-cell lung cancer should be reconsidered."
In a linked Comment, Dr Karen L Reckamp, City of Hope Comprehensive Cancer Center, Duarte, CA, USA, says: "Older patients dominate the lung cancer population, but continue to be under-represented in clinical trials. Additional studies are needed that enrol adequate numbers of older adults, and include a comprehensive geriatric assessment to provide the knowledge required to properly assess the risk–benefit ratio in treatment decisions, so that a personalised approach can be taken."
Professor Elisabeth Quoix, Department of Chest Diseases, Hopitaux Universitaires de Strasbourg, France. T) +33369550897 (please e-mail first to arrange interview) E) equoix@gmail.com
Dr Karen L Reckamp, City of Hope Comprehensive Cancer Center, Duarte, CA, USA.T) +1 626 256-4673 ext 63155 E) kreckamp@coh.org
Journal
The Lancet