78 Dose intensive chemotherapy in patients with advanced small cell lung cancer (SCLC): Preliminary results of a multicenter randomized trial

A 25%–33% increase in initial doses of cisplatin (CDDP) and cyclophosphamide (CPM), when combined with standard doses of doxorubicin and etoposide, has been found sufficient to significantly improve both disease free and overall survival in patients with limited SCLC (NEJM 1993, 329, 1148–1152). In this following trial, we are testing whether or not an increase in dose-intensity of a quite similar 4drug regimen leads to an improvement in survival. From October 1991 to December 1994, 123 patients with untreated SCLC were enrolled in this study comparing “standard dose” (SD) PEVEP for 6 cycles versus “high dose” (HD) PEVEP + rh-GMCSF (E. Coli derived) for 4 cycles. SD PEVEP consisted of: Epirubicin 40 mg/m 2 dl, CDDP 100 mg/m 2 d2, Etoposide 75 mg/m 2 /d dl-3, CPM 400 mg/m 2 /d dl-3. In the HD PEVEP arm the intended doses for each cycle were increased by 50%, except for CDDP: 25%. This HD PEVEP arm was supported by a systematic use ofrh-GMCSF (5 μ g/hg/d s. c.) administered from d4 to dl3. Thus, the cumulative doses in both arms were roughly similar. Responding patients with residual disease confined to the chest were eligible for thoracic radiation. Complete responders were eligible for prophylactic cranial radiation. An interim analysis was performed as planned by the protocol after the inclusion of 50% of 200 patients required to demonstrate a 50% improvement in median survival. Accrual has been closed prematurely on 12/23/94 due to a significant survival difference between the two arms. An updated analysis will be presented.