Karen Kelly, MD

Karen Kelly, MD, sat down to discuss her presentation on when to start immunotherapy in a real world, patient setting.

The cytostatic, molecular-targeted therapies becoming available forlung cancer and other human solid tumors are more likely to result instable disease than to produce tumor regression. In the setting ofadvanced lung cancer, stable disease provides significant benefit to thepatient. However, in the context of clinical trials, stable disease isvaguely defined, difficult to measure, and may represent a heterogeneouspatient population. The inclusion of alternative trial end pointssuch as symptom improvement and biologic activity may help to identifypatients who have achieved clinically relevant stable disease. Theepidermal growth factor receptor–tyrosine kinase inhibitor gefitinib(Iressa) has been shown to produce partial responses and stable diseasein patients with advanced lung cancer who have previously receivedtreatment with standard chemotherapies. In the monotherapy trials ofgefitinib, stable disease was correlated with improvements in diseaserelatedsymptoms and quality of life-the most meaningful end pointsfor the patient with advanced lung cancer. Thus, with the introductionof new molecular-targeted agents, stable disease with clinical benefitshould become an important goal of anticancer therapy.

The majority of individuals diagnosed with lung cancer in theUnited States are 70 years of age and older. Defining appropriatetherapy for older patients with non–small-cell lung cancer (NSCLC) isbecoming a major focus of clinical research. In this article, we reviewthe available data on clinical predictors of risk and benefit for elderlyNSCLC patients receiving treatment via a variety of modalities, includingsurgery, radiotherapy, combined radiotherapy and chemotherapy,and chemotherapy alone. The data demonstrate that subgroups ofelderly patients benefit from appropriately selected treatment. Participationof older patients in clinical trials designed to assess efficacy,toxicity, and quality-of-life outcomes for recently developed treatmentmodalities in this population is critical.

Lung cancer remains the primary cause of cancer-related death in both men and women in the United States. Chemotherapy has been shown to provide a survival benefit in patients with advanced non-small-cell lung cancer (NSCLC), and current regimens have produced median survivals of approximately 8 months and 1-year survival rates of 30% to 35% in patients with stage IIIB and IV disease. Nevertheless, there remains room for improvement. Irinotecan (CPT-11, Camptosar) has demonstrated efficacy in the treatment of small-cell lung cancer (SCLC). It also appears to have promising activity in advanced NSCLC, producing overall response rates of up to 32%. Combinations of irinotecan and cisplatin or carboplatin (Paraplatin) have resulted in overall response rates of 25% to 56% in phase II and III studies in patients with advanced disease, with median survivals ranging from 9 to 13 months and 1-year survival rates of 33% to 58%. Current irinotecan-based doublet and triplet regimens appear to produce promising response rates with manageable toxicities. In addition, irinotecan has demonstrated potential as a radiosensitizing agent and is currently being evaluated in several trials of combined-modality therapy in patients with locally advanced NSCLC. Early trials of irinotecan in combination with cisplatin or carboplatin along with radiation therapy have reported overall response rates of 60% to 67%. The approach appears to have potential and warrants further study. [ONCOLOGY 16:1153-1168, 2002]