Results of 27 years of phase III trials for patients with extensive-disease small-cell lung cancer

Abstract

e19021 Background: Few studies have formally assessed whether treatment outcomes for patients with extensive-disease small-cell lung cancer (ED-SCLC) enrolled in Phase III trials have improved substantially over the years. This investigation determined the trends in the outcomes for the patients in those trials. Methods: We analyzed trials that were reported between January 1991 and August 2008. Phase III randomized controlled trials were eligible if they compared first-line, systemic chemotherapy for ED-SCLC. Data were evaluated using linear regression analysis. Results: We identified 55 trials initiated between 1980 and 2006, involving 10,407 patients with 116 chemotherapy arms. The number of randomized patients and the proportions of patients with good performance status (PS) increased with the passage of time. In the 1990s, increasing numbers of studies examined cisplatin-based regimens, especially cisplatin and etoposide (PE) regimens, while decreasing numbers examined cyclophosphamide, doxorubicin, and vincristine-based regimens. A scattergram of the parameters ‘year of trial initiation’ and ‘median survival time’ (MST) indicated that MST increased 0.024 months (0.71 days) per year (P = 0.198). The multiple regression analysis showed no significant survival improvement over the years (regression coefficient for the year of trial initiation = 0.004, P = 0.980). In addition, the use of PE regimens did not prolong survival, whilst the proportion of good PS patients and the assignment of prophylactic cranial irradiation were significantly associated with favorable outcomes. Conclusions: The survival of patients with ED-SCLC enrolled in phase III trials has not improved significantly over the years, suggesting the need for a breakthrough, such as the discovery of novel molecular targets. No significant financial relationships to disclose.