Third-Line Chemotherapy in Small-Cell Lung Cancer: An International Analysis

The benefit of third-line chemotherapy for small-cell lung cancer (SCLC) is largely unknown. We reviewed 120 patient records to identify response rates and survival after third-line therapy. The overall response rate and survival benefit were generally modest, however, response in the second-line and normal baseline lactate dehydrogenase (LDH) levels might predict for better outcomes after third-line treatment. Introduction: Small-cell lung cancer is an aggressive disease for which the mainstay of treatment is chemotherapy. Despite good initial responses most patients will relapse. Some will receive second-line therapy with clinical benefit, but for third-line chemotherapy there is little evidence to guide treatment decisions and the benefits of treatment are unknown. This study investigated the treatment of SCLC in the third-line setting. Patients and Methods: An international, multicenter retrospective analysis of patients who received at least 3 lines of chemotherapy for their SCLC was performed. Results: From 2000 to 2010, 120 patients were identified from 5 centers: median age 61, 40% (n = 72) limited stage, and 79% (n = 95) Eastern Cooperative Oncology Group performance status of 0 to 1. Only 22% of these patients received 3 distinct lines of chemotherapy. The remainder were rechallenged with a chemotherapy regimen used at least once previously. Six percent received platinum-based chemotherapy in all 3 lines. In third-line, response rate was 18% and median overall survival was 4.7 months. Factors associated with longer survival included normal baseline LDH levels and response to second-line chemotherapy. On multivariate analysis only normal baseline LDH retained statistical significance. Thirty-five patients went on to receive chemotherapy beyond the third line. Conclusion: Few SCLC patients receive 3 chemotherapy lines. Most patients were rechallenged with a similar regimen at least once. Response and survival in the third-line setting are modest. Lack of response to second-line chemotherapy and elevated baseline LDH level might predict lack of benefit from third-line treatment. This data set does not include patients receiving fewer lines for comparison. (C) 2014 Elsevier Inc. All rights reserved.