Neglected and underrepresented subpopulations: elderly and performance status 2 patients with advanced-stage non-small-cell lung cancer.

Elderly patients and those with performance status (PS) of 2 with non-small-cell lung cancer (NSCLC) have been habitually underrepresented in clinical trials. Therapeutic neglect and legitimate concerns about toxicity are responsible. Yet randomized phase III data in the elderly have demonstrated a survival benefit for single-agent chemotherapy compared with best supportive care, and retrospective analyses of fit elderly patients enrolled on platinum agent-based trials have shown similar survival rates, albeit more toxicity, compared with younger counterparts. To date, however, there are no phase III trials specific to the elderly population demonstrating a survival benefit for platinum agent-based combinations compared with the constituent nonplatinum single agent; such efforts are ongoing. Performance status is a critical prognostic factor in advanced-stage NSCLC. Retrospective analyses of multiple trials conducted before 1995 suggested that patients with advanced-stage NSCLC and compromised PS experienced substantial toxicity and virtually no benefit from systemic chemotherapy, leading most cooperative groups to suspend research in this cohort. But this trend has changed. A subset analysis of patients with a PS of 2 enrolled on a recent Cancer and Leukemia Group B trial showed a significant survival benefit for carboplatin in combination with paclitaxel compared with paclitaxel alone, and recent randomized phase II efforts evaluating platinum agent-based combinations have yielded median survival times of > 6 months with acceptable toxicity rates. Although the Selective Targeting for Efficacy in Lung Cancer, Lower Adverse Reaction trials testing polyglutamated paclitaxel failed to show a survival advantage compared with standard agents, interest in testing new, less toxic agents continues. Future efforts will need to differentiate the reasons for compromised PS, be it tumor burden, comorbidity, or both.