A prospective randomized phase III, double-blind, placebo-controlled study of thalidomide in extended-disease (ED) SCLC patients after response to chemotherapy (CT): An intergroup study FNCLCC Cleo04 - IFCT 00–01

Abstract

7057 Background: This study aimed at determining whether or not thalidomide prolongs survival of patients (pts) suffering from SCLC. Methods: Eligibility consisted of previously untreated ED-SCLC, age <70 years, PS ≤2, weight loss <10% and, for women, post-menopausal status. Pts were registered in the study and received two courses of PCDE given 4 weeks apart with G-CSF primary prophylaxis recommended. Afterwards, pts who experienced a response were randomized to receive four additional cycles of PCDE plus thalidomide, (400 mg daily) or placebo. The planned accrual was 200 randomised pts in order to detect a 20% survival improvement. Results: The study was shortened with final analysis performed taking into account 119 registered pts (low accrual). There were 4 toxic-deaths (3.3%). Tumour assessment performed after the first two CT courses demonstrated 11 complete responders and 86 partial responders (81.4% overall response rate). Among these pts, 92 were randomly assigned, 49 in the thalidomide group and 43 in placebo group. The 5 remaining pts were not randomised due to poor recovery from previous CT. Pre-study pts’ characteristics did not differ between the two groups. The planned six cycles of PCDE were delivered to an equal proportion of pts in both groups (75.5% versus 74.4%). Mean ± SD exposure duration to thalidomide was 4.5 months ± 2.7 and to placebo 5.1 ± 2.4 (NS). Reasons for withdrawal differed between the two groups with toxicity as main reason for thalidomide (55.3% versus 35%) and disease progression as main reason for placebo (43% versus 62%; p = 0.06). In Cox model of overall survival within the 9 months following randomisation, pts allocated to the thalidomide group had the longest survival (HR of death for pts in the thalidomide group: 0.48 [95% CI: 0.24–0.93]; p = 0.03; median survival from randomisation: 11.7 versus 8.7 months for thalidomide and placebo groups respectively); Conclusion: Thalidomide prolongs survival of pts with SCLC after response to CT. This study is a clue in favour of angiogenesis process as therapeutic window in SCLC therapy. Supported by the French League against Cancer. No significant financial relationships to disclose.